Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive ...Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.展开更多
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b...Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely over...Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely overlooked in the past because it is generally less impaired in the early stages of PD than in Alzheimer's disease.展开更多
Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated tha...Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated that melatonin and dopamine alleviated waterlogging by removing reactive oxygen species(ROS),and that the nitric oxide(NO)content and nitrate reductase(NR)activity were significantly correlated.Melatonin and dopamine were also found to recruit different candidate beneficial endophytes(melatonin:Novosphingobium,Propionivibrio,and Cellvibrio;dopamine:Hydrogenophaga,Simplicispira,Methyloversatilis,Candidatus_Kaiserbacteria,and Humicola),and these endophytes were significantly and positively correlated with plant growth.Network analyses showed that melatonin and dopamine significantly affected the endophytic bacterial and fungal communities under waterlogging stress.The metabolomic results showed that melatonin and dopamine led to waterlogging resistance by upregulating the abundance of beneficial substances such as amino acids,flavonoids,coumarins,and organic acids.In addition,melatonin and dopamine regulated the physicochemical properties of the soil,which altered the endophyte community and affected plant growth.The co-occurrence network demonstrated close and complex relationships among endophytes,metabolites,soil,and the plants.Our results demonstrate that melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience.This study provides new insights into how melatonin and dopamine alleviate stress and a theoretical basis for synergistic beneficial microbial resistance to waterlogging stress.展开更多
Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing counte...Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing countermeasures cannot effectively address this challenge.Here,we used Malus hupehensis as a test organism to investigate whether the pleiotropic molecule dopamine can alleviate ARD using pot experiments.Exogenous application of 100μmol L-1 dopamine significantly promoted the growth of apple seedlings in the replanted soil,with a relative growth rate increase of 17.44%.Our results revealed two major pathways by which dopamine regulates ARD resistance in apple trees.First,dopamine effectively reduces the level of ROS and activates the expression of genes related to nitrogen(N)transport and metabolism.Among those genes,MdNLP5,MdNRT1.1,MdNLP2,MdNRT2.5,MdNLP3,MdNRT2.4,MdNADH-GAGOT,and MdFd-GAGOT were strongly regulated by dopamine.These regulatory effects promoted the uptake and utilization of soil N by the plants.Second,dopamine improved the physical and chemical properties,enhanced microbial community diversity,and promoted mutual cooperation between microbial communities in the soil.Furthermore,dopamine altered the microbial structure of rhizosphere soil(upregulating Clostridiales,Gaiellales,Sordariales and Mortierellales;downregulating Micrococcales,Longimicrobiales,Hypocreales and Cystobasidiales).Notably,dopamine significantly upregulated the abundances of Gaiella and Mortierella,both of which were positively correlated with soil urease activity,soil available N content,plant growth and N uptake.Dopamine also significantly downregulated the abundance of the plant pathogen Gibberella(by 11.71-fold)in replant soil.Our results provide insights into the mechanisms by which dopamine promotes ARD resistance,and can promote the sustainable development of the apple industry.展开更多
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
A novel strategy was developed to prepare the methacrylic gelatin-dopamine(GelMA-DA)/Ag nanoparticles(NPs)/graphene oxide(GO) composite hydrogels with good biocompatibility,mechanical properties,and antibacterial acti...A novel strategy was developed to prepare the methacrylic gelatin-dopamine(GelMA-DA)/Ag nanoparticles(NPs)/graphene oxide(GO) composite hydrogels with good biocompatibility,mechanical properties,and antibacterial activity.Mussel-inspired DA was utilized to modify the GelMA molecules,which imparts good adhesive performance to the hydrogels.GO,interfacial enhancer,not only improves mechanical properties of the hydrogels,but also provides anchor sites for loading Ag NPs through numerous oxygencontaining functional groups on the surface.The experimental results show that the GelMA/Ag NPs/GO hydrogels have good biocompatibility,and exhibit a swelling rate of 202±16%,the lap shear strength of 147±17 kPa,and compressive modulus of 136±53 kPa,in the case of the Ag NPs/GO content of 2 mg/mL.Antibacterial activity of the hydrogels against both gram-negative and gram-positive bacteria is dependent on the Ag NPs/GO content derived from the release of Ag^(+).Furthermore,the GelMA/Ag NPs/GO hydrogels possess good adhesive ability,which is resistant to highly twisted state when stuck on the surface of pigskin.These results demonstrate promising potential of the GelMA-DA/Ag NPs/GO hydrogels as wound dressings for biomedical applications in clinical and emergent treatment.展开更多
Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histo...Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.展开更多
AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,a...AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.展开更多
Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relations...Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.展开更多
The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is the...The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.展开更多
Dopamine has demonstrated promise as a stress-relief substance.However,the function of dopamine in Cd tolerance and its mechanism remains largely unknown.The current study was performed to investigate the mechanism of...Dopamine has demonstrated promise as a stress-relief substance.However,the function of dopamine in Cd tolerance and its mechanism remains largely unknown.The current study was performed to investigate the mechanism of dopamine on alleviating apple Cd stress through regular application of CdCl2 and dopamine solution to potting soil.The results indicated that dopamine significantly reduced reactive oxygen species(ROS)and Cd accumulation and alleviated the inhibitory effect of Cd stress on the growth of apple plants through activation of the antioxidant system,enhancement of photosynthetic capacity,and regulation of gene expression related to Cd absorption and detoxification.The richness of the rhizosphere microbial community increased,and community composition and assembly were affected by dopamine treatment.Network analysis of microbial communities showed that the numbers of nodes and total links increased significantly after dopamine treatment,while the keystone species shifted.Linear discriminant analysis effect size indicated that some biomarkers were significantly enriched after dopamine treatment,suggesting that dopamine induced plants to recruit potentially beneficial microorganisms(Pseudoxanthomonas,Aeromicrobium,Bradyrhizobium,Frankia,Saccharimonadales,Novosphingobium,and Streptomyces)to resist Cd stress.The co-occurrence network showed several metabolites that were positively correlated with relative growth rate and negatively correlated with Cd accumulation,suggesting that potentially beneficial microorganisms may be attracted by several metabolites(L-threonic acid,profenamine,juniperic acid and(3β,5ξ,9ξ)-3,6,19-trihydroxyurs-12-en-28-oic acid).Our results demonstrate that dopamine alleviates Cd stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed.This study provides an effective means to reduce the harm to agricultural production caused by heavy metals.展开更多
BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brai...BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain.However,recent studies have shown that DARPP-32 is also expressed in other tissues,including colorectal cancer(CRC),where its function is not well understood.AIM To explore the effect of DARPP-32 on CRC progression.METHODS The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays.The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays,while apoptosis was measured by flow cytometry.The migratory and invasive potential of CRC cell lines were deter-mined using wound healing and transwell chamber assays.In vivo studies involved monitoring the growth rate of xenograft tumors.Finally,the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.RESULTS DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC.Overexpression of DARPP-32 was shown to promote cancer cell proliferation,migration,and invasion and reduce apoptosis.DARPP-32 knockdown resulted in the opposite functional effects.Mechanistically,DARPP-32 may regulate the phosphoinositide 3-kinase(PI3K)/AKT signaling pathway in order to carry out its biological function.CONCLUSION DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.展开更多
Astrocytes and astrocyte-related proteins play important roles in maintaining normal brain function,and also regulate pathological processes in brain diseases and injury.However,the role of astrocytes in the dopamine-...Astrocytes and astrocyte-related proteins play important roles in maintaining normal brain function,and also regulate pathological processes in brain diseases and injury.However,the role of astrocytes in the dopamine-depleted striatum remains unclear.A rat model of Parkinson’s disease was therefore established by injecting 10μL 6-hydroxydopamine(2.5μg/μL)into the right medial forebrain bundle.Immunohistochemical staining was used to detect the immunoreactivity of glial fibrillary acidic protein(GFAP),calcium-binding protein B(S100B),and signal transducer and activator of transcription 3(STAT3)in the striatum,and to investigate the co-expression of GFAP with S100B and STAT3.Western blot assay was used to measure the protein expression of GFAP,S100B,and STAT3 in the striatum.Results demonstrated that striatal GFAP-immunoreactive cells had an astrocytic appearance under normal conditions,but that dopamine depletion induced a reactive phenotype with obvious morphological changes.The normal striatum also contained S100B and STAT3 expression.S100B-immunoreactive cells were uniform in the striatum,with round bodies and sparse,thin processes.STAT3-immunoreactive cells presented round cell bodies with sparse processes,or were darkly stained with a large cell body.Dopamine deprivation induced by 6-hydroxydopamine significantly enhanced the immunohistochemical positive reaction of S100B and STAT3.Normal striatal astrocytes expressed both S100B and STAT3.Striatal dopamine deprivation increased the number of GFAP/S100B and GFAP/STAT3 double-labeled cells,and increased the protein levels of GFAP,S100B,and STAT3.The present results suggest that morphological changes in astrocytes and changes in expression levels of astrocyte-related proteins are involved in the pathological process of striatal dopamine depletion.The study was approved by Animal Care and Use Committee of Sun Yat-sen University,China(Zhongshan Medical Ethics 2014 No.23)on September 22,2014.展开更多
Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viabilit...Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viability was processed when treated with 50 μmol·L^-1 of dopamine for 24 h by MTT assay. Early apoptosis, late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide （PI） double-staining, respectively. Generation of reactive oxygen species （ROS） was assessed by DCFH-DA, an oxidation-sensitive fluorescent probe. To evaluate mitochondrion membrane potential （Δψm） using flow cytometry with the fluorescent dye Rhodamine 123. The transcriptional level of P53 was studied using RT- PCR. Results The dopamine-induced loss of cell viability was significantly attenuated by liriodendrin treatment at the concentration of 10^-8, 10^-7, 10^-6, 10^-5 and 10^-4 mol·L^-1. The protective effects of liriodendrin （10^-7, 10^-6 and 10^-5 mol·L^-1） on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level and anti-apoptotic effect via protection of Δψm. In addition, the effect of liriodendrin may involve the P53 pathway in apoptosis. Conclusion Liriodendrin may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases such as Parkinson＇s disease （PD）展开更多
Objective To investigate the influence of dopamine （DA） and DA receptor＇s antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influen...Objective To investigate the influence of dopamine （DA） and DA receptor＇s antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influence of DA on the electric activity of the pain-excited neuron （PEN） in the caudate nucleus （Cd） of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated. Results DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats. Conclusion The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.展开更多
To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa ,this study investigated the effects of dopamine (DA),estradiol (E 2) and testosterone (T) on the in vitro release of luteiniz...To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa ,this study investigated the effects of dopamine (DA),estradiol (E 2) and testosterone (T) on the in vitro release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary fragments of female Rana rugulosa using a static incubation system and radio immunoassay (RIA). The results indicated that DA at the concentration from 0 1?μmol/L to 10?μmol/L inhibited the release of LH and FSH from the pituitary fragments of sexually pre mature or hibernating individuals,and the inhibitory effects enhanced with increasing concentrations of DA. E 2 at 1?μmol/L and 10?μmol/L significantly stimulated the release of LH of sexually pre mature individuals,but inhibited their FSH release at 0 1?μmol/L to 10?μmol/L;T had no obvious effects on their FSH release,but significantly inhibited their LH release at 10?μmol/L. Neither E 2 nor T,at the concentration from 0 1?μmol/L to 100?μmol/L,had obvious effects on the release of LH and FSH of hibernating individuals. The data suggest that DA and sexual steroids may have direct regulatory actions on LH and FSH release at the pituitary level in Rana rugulosa ,and the action of sexual steroids may relate to the gonadal development stages (seasons).展开更多
Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be ...Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites in the striatum.To further explore the neuroprotective effect of ginsenoside Rbl against lipopolysaccharide-induced neurotoxicity,immunohistochemistry and western blot assay of tyrosine hydroxylase were performed to evaluate dopaminergic neuron degeneration in the substantial nigra par compacta.The results showed that lipopolysaccharide injection caused a large loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra and a significant decrease in overall tyrosine hydroxylase expression.However,ginsenoside Rb1 noticeably reversed these changes.To investigate whether the neuroprotective effect of ginsenoside Rbl was associated with inhibition of lipopolysaccharide-induced microglial activation,we examined expression of the microglia marker Iba-1.Our results confirmed that lipopolysaccharide injection induced a significant increase in Iba-1 expression in the substantia nigra;however,ginsenoside Rbl effectively suppressed lipopolysaccharide-induced microglial overactivation.To elucidate the inhibitory mechanism of ginsenoside Rb1,we examined expression levels of inflammatory mediators(tumor necrosis factor-a,interleukin-1β,inducible nitric oxide synthase,and cyclooxygenase 2)and phosphorylation of nuclear factor kappa B signaling-related proteins(IκB,IKK)in the substantia nigra with enzyme-linked immunosorbent and western blot assays.Our results revealed that compared with the control group,phosphorylation and expression of inflammatory mediators IκB and IKK in the substantia nigra of lipopolysaccharide group rats were significantly increased;whereas,ginsenoside Rbl obviously reduced lipopolysaccharide-induced changes on the lesioned side of the substantial nigra par compacta.These findings confirm that ginsenoside Rbl can inhibit inflammation induced by lipopolysaccharide injection into the substantia nigra and protect dopaminergic neurons,which may be related to its inhibition of the nuclear factor kappa B signaling pathway.This study was approved by the Experimental Animal Ethics Committee of Shandong University of China in April 2016(approval No.KYLL-2016-0148).展开更多
The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesi...The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders, in particular Parkinson’s disease, which are associated with a subtle and chronic inflammatory response. A substantial body of evidence has demonstrated the non-neuronal expression of dopamine, its receptors and of the machinery that governs synthesis, secretion and storage of dopamine across several immune cell types. This review aims to summarize current knowledge on the role and expression of dopamine in immune cells. One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine, in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease. A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation. These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.展开更多
基金supported by the National Natural Science Foundation of China,No.82101263Jiangsu Province Science Foundation for Youths,No.BK20210903Research Foundation for Talented Scholars of Xuzhou Medical University,No.RC20552114(all to CT)。
文摘Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.
文摘Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by the STI 2030-Major Projects,No.2021ZD0200500the Natural Science Foundation of Shanghai,No.21ZR1419700(both to SL)。
文摘Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely overlooked in the past because it is generally less impaired in the early stages of PD than in Alzheimer's disease.
基金supported by the National Natural Science Foundation of China(31901964)the Natural Science Foundation of Hebei,China(C2021204158)+3 种基金the Science and Technology Project of Hebei Education Department,China(BJK2022012)the Introduced Talents Project of Hebei Agricultural University,China(YJ201904)the earmarked fund for Hebei Apple Innovation Team of Modern Agroindustry Technology Research System,China(HBCT2024150205)the earmarked fund for the China Agricultural Research System,China(CARS-27).
文摘Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated that melatonin and dopamine alleviated waterlogging by removing reactive oxygen species(ROS),and that the nitric oxide(NO)content and nitrate reductase(NR)activity were significantly correlated.Melatonin and dopamine were also found to recruit different candidate beneficial endophytes(melatonin:Novosphingobium,Propionivibrio,and Cellvibrio;dopamine:Hydrogenophaga,Simplicispira,Methyloversatilis,Candidatus_Kaiserbacteria,and Humicola),and these endophytes were significantly and positively correlated with plant growth.Network analyses showed that melatonin and dopamine significantly affected the endophytic bacterial and fungal communities under waterlogging stress.The metabolomic results showed that melatonin and dopamine led to waterlogging resistance by upregulating the abundance of beneficial substances such as amino acids,flavonoids,coumarins,and organic acids.In addition,melatonin and dopamine regulated the physicochemical properties of the soil,which altered the endophyte community and affected plant growth.The co-occurrence network demonstrated close and complex relationships among endophytes,metabolites,soil,and the plants.Our results demonstrate that melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience.This study provides new insights into how melatonin and dopamine alleviate stress and a theoretical basis for synergistic beneficial microbial resistance to waterlogging stress.
基金supported by National Natural Science Foundation of China(31901964)the Science and Technology Project of Hebei Education Department,China(BJK2022012)+3 种基金the Innovation Ability Training Project for Graduate Student of Hebei Province,China(CXZZBS2023071)the Introduced Talents Project of Hebei Agricultural University,China(YJ201904)the Key Research and Development Project of Hebei Province,China(21326308D-02-03)the Earmarked Fund for the China Agricultural Research System,China(CARS-27).
文摘Apple replant disease(ARD)is a complex agricultural problem caused by multiple stressors that can lead to increased reactive oxygen species(ROS)levels and limited nutrient utilization in plants.However,existing countermeasures cannot effectively address this challenge.Here,we used Malus hupehensis as a test organism to investigate whether the pleiotropic molecule dopamine can alleviate ARD using pot experiments.Exogenous application of 100μmol L-1 dopamine significantly promoted the growth of apple seedlings in the replanted soil,with a relative growth rate increase of 17.44%.Our results revealed two major pathways by which dopamine regulates ARD resistance in apple trees.First,dopamine effectively reduces the level of ROS and activates the expression of genes related to nitrogen(N)transport and metabolism.Among those genes,MdNLP5,MdNRT1.1,MdNLP2,MdNRT2.5,MdNLP3,MdNRT2.4,MdNADH-GAGOT,and MdFd-GAGOT were strongly regulated by dopamine.These regulatory effects promoted the uptake and utilization of soil N by the plants.Second,dopamine improved the physical and chemical properties,enhanced microbial community diversity,and promoted mutual cooperation between microbial communities in the soil.Furthermore,dopamine altered the microbial structure of rhizosphere soil(upregulating Clostridiales,Gaiellales,Sordariales and Mortierellales;downregulating Micrococcales,Longimicrobiales,Hypocreales and Cystobasidiales).Notably,dopamine significantly upregulated the abundances of Gaiella and Mortierella,both of which were positively correlated with soil urease activity,soil available N content,plant growth and N uptake.Dopamine also significantly downregulated the abundance of the plant pathogen Gibberella(by 11.71-fold)in replant soil.Our results provide insights into the mechanisms by which dopamine promotes ARD resistance,and can promote the sustainable development of the apple industry.
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
基金Funded by the National Key Research and Development(R&D) Program of China(No.2018YFB1105702)。
文摘A novel strategy was developed to prepare the methacrylic gelatin-dopamine(GelMA-DA)/Ag nanoparticles(NPs)/graphene oxide(GO) composite hydrogels with good biocompatibility,mechanical properties,and antibacterial activity.Mussel-inspired DA was utilized to modify the GelMA molecules,which imparts good adhesive performance to the hydrogels.GO,interfacial enhancer,not only improves mechanical properties of the hydrogels,but also provides anchor sites for loading Ag NPs through numerous oxygencontaining functional groups on the surface.The experimental results show that the GelMA/Ag NPs/GO hydrogels have good biocompatibility,and exhibit a swelling rate of 202±16%,the lap shear strength of 147±17 kPa,and compressive modulus of 136±53 kPa,in the case of the Ag NPs/GO content of 2 mg/mL.Antibacterial activity of the hydrogels against both gram-negative and gram-positive bacteria is dependent on the Ag NPs/GO content derived from the release of Ag^(+).Furthermore,the GelMA/Ag NPs/GO hydrogels possess good adhesive ability,which is resistant to highly twisted state when stuck on the surface of pigskin.These results demonstrate promising potential of the GelMA-DA/Ag NPs/GO hydrogels as wound dressings for biomedical applications in clinical and emergent treatment.
基金supported by an under-40 grant from the Italian Association for Alzheimer’s Research [AIRALZH AGYR2021]the Strategic University Projects–Young Researcher Independence grant [YRG2021] from the Università Campus Bio-Medico di Roma (Rome, Italy)(to LLB)+1 种基金Italian Ministry of Health [Research Grant:GR-2019-12370446]the American Alzheimer’s Association [AARG-22-922961](to PK)。
文摘Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.
文摘AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.
基金supported by the National Natural Science Foundation of China,Nos. 81971006 (to DSG), 82101263 (to CXT)Jiangsu Province Science Foundation for Youths,No. BK20210903 (to CXT)+2 种基金Research Foundation for Talented Scholars of Xuzhou Medical University,No. RC20552114 (to CXT)Science&Technology Program of Xuzhou,No. KC19016 (to JC)Project of Xuzhou Medical University,No. 2018KJ06 (to JC)。
文摘Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.
文摘The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.
基金This work was supported by the National Natural Science Foundation of China(No.31901964)the Science and Technology Project of Hebei Education Department(No.BJK2022012)the Earmarked fund for the China Agricultural Research System(No.CARS-27).
文摘Dopamine has demonstrated promise as a stress-relief substance.However,the function of dopamine in Cd tolerance and its mechanism remains largely unknown.The current study was performed to investigate the mechanism of dopamine on alleviating apple Cd stress through regular application of CdCl2 and dopamine solution to potting soil.The results indicated that dopamine significantly reduced reactive oxygen species(ROS)and Cd accumulation and alleviated the inhibitory effect of Cd stress on the growth of apple plants through activation of the antioxidant system,enhancement of photosynthetic capacity,and regulation of gene expression related to Cd absorption and detoxification.The richness of the rhizosphere microbial community increased,and community composition and assembly were affected by dopamine treatment.Network analysis of microbial communities showed that the numbers of nodes and total links increased significantly after dopamine treatment,while the keystone species shifted.Linear discriminant analysis effect size indicated that some biomarkers were significantly enriched after dopamine treatment,suggesting that dopamine induced plants to recruit potentially beneficial microorganisms(Pseudoxanthomonas,Aeromicrobium,Bradyrhizobium,Frankia,Saccharimonadales,Novosphingobium,and Streptomyces)to resist Cd stress.The co-occurrence network showed several metabolites that were positively correlated with relative growth rate and negatively correlated with Cd accumulation,suggesting that potentially beneficial microorganisms may be attracted by several metabolites(L-threonic acid,profenamine,juniperic acid and(3β,5ξ,9ξ)-3,6,19-trihydroxyurs-12-en-28-oic acid).Our results demonstrate that dopamine alleviates Cd stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed.This study provides an effective means to reduce the harm to agricultural production caused by heavy metals.
基金Supported by Chongqing Key Diseases Research and Application Demonstration Program,No.2019ZX003General Project of Chongqing Nature Science Foundation,No.cstc2021jcyj-msxmX0283.
文摘BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain.However,recent studies have shown that DARPP-32 is also expressed in other tissues,including colorectal cancer(CRC),where its function is not well understood.AIM To explore the effect of DARPP-32 on CRC progression.METHODS The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays.The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays,while apoptosis was measured by flow cytometry.The migratory and invasive potential of CRC cell lines were deter-mined using wound healing and transwell chamber assays.In vivo studies involved monitoring the growth rate of xenograft tumors.Finally,the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.RESULTS DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC.Overexpression of DARPP-32 was shown to promote cancer cell proliferation,migration,and invasion and reduce apoptosis.DARPP-32 knockdown resulted in the opposite functional effects.Mechanistically,DARPP-32 may regulate the phosphoinositide 3-kinase(PI3K)/AKT signaling pathway in order to carry out its biological function.CONCLUSION DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.
基金supported by the National Natural Science Foundation of China,No.81471288(to WLL)the National High Technology Research and Development Program of China(863 Program),No.2017YFA0104704(to WLL)
文摘Astrocytes and astrocyte-related proteins play important roles in maintaining normal brain function,and also regulate pathological processes in brain diseases and injury.However,the role of astrocytes in the dopamine-depleted striatum remains unclear.A rat model of Parkinson’s disease was therefore established by injecting 10μL 6-hydroxydopamine(2.5μg/μL)into the right medial forebrain bundle.Immunohistochemical staining was used to detect the immunoreactivity of glial fibrillary acidic protein(GFAP),calcium-binding protein B(S100B),and signal transducer and activator of transcription 3(STAT3)in the striatum,and to investigate the co-expression of GFAP with S100B and STAT3.Western blot assay was used to measure the protein expression of GFAP,S100B,and STAT3 in the striatum.Results demonstrated that striatal GFAP-immunoreactive cells had an astrocytic appearance under normal conditions,but that dopamine depletion induced a reactive phenotype with obvious morphological changes.The normal striatum also contained S100B and STAT3 expression.S100B-immunoreactive cells were uniform in the striatum,with round bodies and sparse,thin processes.STAT3-immunoreactive cells presented round cell bodies with sparse processes,or were darkly stained with a large cell body.Dopamine deprivation induced by 6-hydroxydopamine significantly enhanced the immunohistochemical positive reaction of S100B and STAT3.Normal striatal astrocytes expressed both S100B and STAT3.Striatal dopamine deprivation increased the number of GFAP/S100B and GFAP/STAT3 double-labeled cells,and increased the protein levels of GFAP,S100B,and STAT3.The present results suggest that morphological changes in astrocytes and changes in expression levels of astrocyte-related proteins are involved in the pathological process of striatal dopamine depletion.The study was approved by Animal Care and Use Committee of Sun Yat-sen University,China(Zhongshan Medical Ethics 2014 No.23)on September 22,2014.
基金National Natural Sciences Foundation of China(Grant No.30370720and No.30572343)Nationa l973 Fundamental Project of China(No.2004CB518906)
文摘Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viability was processed when treated with 50 μmol·L^-1 of dopamine for 24 h by MTT assay. Early apoptosis, late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide （PI） double-staining, respectively. Generation of reactive oxygen species （ROS） was assessed by DCFH-DA, an oxidation-sensitive fluorescent probe. To evaluate mitochondrion membrane potential （Δψm） using flow cytometry with the fluorescent dye Rhodamine 123. The transcriptional level of P53 was studied using RT- PCR. Results The dopamine-induced loss of cell viability was significantly attenuated by liriodendrin treatment at the concentration of 10^-8, 10^-7, 10^-6, 10^-5 and 10^-4 mol·L^-1. The protective effects of liriodendrin （10^-7, 10^-6 and 10^-5 mol·L^-1） on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level and anti-apoptotic effect via protection of Δψm. In addition, the effect of liriodendrin may involve the P53 pathway in apoptosis. Conclusion Liriodendrin may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases such as Parkinson＇s disease （PD）
文摘Objective To investigate the influence of dopamine （DA） and DA receptor＇s antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influence of DA on the electric activity of the pain-excited neuron （PEN） in the caudate nucleus （Cd） of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated. Results DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats. Conclusion The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.
文摘To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa ,this study investigated the effects of dopamine (DA),estradiol (E 2) and testosterone (T) on the in vitro release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary fragments of female Rana rugulosa using a static incubation system and radio immunoassay (RIA). The results indicated that DA at the concentration from 0 1?μmol/L to 10?μmol/L inhibited the release of LH and FSH from the pituitary fragments of sexually pre mature or hibernating individuals,and the inhibitory effects enhanced with increasing concentrations of DA. E 2 at 1?μmol/L and 10?μmol/L significantly stimulated the release of LH of sexually pre mature individuals,but inhibited their FSH release at 0 1?μmol/L to 10?μmol/L;T had no obvious effects on their FSH release,but significantly inhibited their LH release at 10?μmol/L. Neither E 2 nor T,at the concentration from 0 1?μmol/L to 100?μmol/L,had obvious effects on the release of LH and FSH of hibernating individuals. The data suggest that DA and sexual steroids may have direct regulatory actions on LH and FSH release at the pituitary level in Rana rugulosa ,and the action of sexual steroids may relate to the gonadal development stages (seasons).
基金supported by the Medical and Health Technology Development Plan of Shandong Province of China,No.2011HD009(to AHW)the Chinese Medicine Science and Technology Development Plan Project of Shandong Province of China,No.2017-163(to AHW)+1 种基金the Natural Science Foundation of Shandong Province of China,No.ZR2016HP23(to AHW)the Science and Technology Development Plan Project of Taian City of China,No.2017NS0151(to XCS)
文摘Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites in the striatum.To further explore the neuroprotective effect of ginsenoside Rbl against lipopolysaccharide-induced neurotoxicity,immunohistochemistry and western blot assay of tyrosine hydroxylase were performed to evaluate dopaminergic neuron degeneration in the substantial nigra par compacta.The results showed that lipopolysaccharide injection caused a large loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra and a significant decrease in overall tyrosine hydroxylase expression.However,ginsenoside Rb1 noticeably reversed these changes.To investigate whether the neuroprotective effect of ginsenoside Rbl was associated with inhibition of lipopolysaccharide-induced microglial activation,we examined expression of the microglia marker Iba-1.Our results confirmed that lipopolysaccharide injection induced a significant increase in Iba-1 expression in the substantia nigra;however,ginsenoside Rbl effectively suppressed lipopolysaccharide-induced microglial overactivation.To elucidate the inhibitory mechanism of ginsenoside Rb1,we examined expression levels of inflammatory mediators(tumor necrosis factor-a,interleukin-1β,inducible nitric oxide synthase,and cyclooxygenase 2)and phosphorylation of nuclear factor kappa B signaling-related proteins(IκB,IKK)in the substantia nigra with enzyme-linked immunosorbent and western blot assays.Our results revealed that compared with the control group,phosphorylation and expression of inflammatory mediators IκB and IKK in the substantia nigra of lipopolysaccharide group rats were significantly increased;whereas,ginsenoside Rbl obviously reduced lipopolysaccharide-induced changes on the lesioned side of the substantial nigra par compacta.These findings confirm that ginsenoside Rbl can inhibit inflammation induced by lipopolysaccharide injection into the substantia nigra and protect dopaminergic neurons,which may be related to its inhibition of the nuclear factor kappa B signaling pathway.This study was approved by the Experimental Animal Ethics Committee of Shandong University of China in April 2016(approval No.KYLL-2016-0148).
基金supported by a Research Development Fund(UTS Start-Up Grant 2018)from the University of Technology Sydney to AC。
文摘The dopaminergic system controls several vital central nervous system functions, including the control of movement, reward behaviors and cognition. Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders, in particular Parkinson’s disease, which are associated with a subtle and chronic inflammatory response. A substantial body of evidence has demonstrated the non-neuronal expression of dopamine, its receptors and of the machinery that governs synthesis, secretion and storage of dopamine across several immune cell types. This review aims to summarize current knowledge on the role and expression of dopamine in immune cells. One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine, in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease. A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation. These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.
