T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and addition...T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.展开更多
Orexin has several biological functions, including the regulation of reproductive endocrine signaling, which has received much attention. However, little is known about the mechanism through which orexin regulates the...Orexin has several biological functions, including the regulation of reproductive endocrine signaling, which has received much attention. However, little is known about the mechanism through which orexin regulates the levels of neuroendocrine hormones and peptides. We injected orexin A or physiological saline into the lateral ventricle of 10 ovariectomized (OVX) gilts, and determined the subsequent changes in serum luteinizing hormone (LH) concentration by using radioimmunoassay (RIA). We also examined the expression of GnRH, NPY, and POMC mRNAs in the hypothalamus and that of LH, folliclestimulating hormone (FSH), POMC, and ghrelin mRNAs in the pituitary by using semi-quantitative reverse transcription polymerase chain reaction. We found the following results: (1) Orexin A transiently promoted LH secretion; serum LH concentration started to increase at 10 min after the orexin injection, peaked at 30 min, and returned to its initial level at 1.5 h; (2) orexin A upregulated GnRH mRNA expression and downregulated NPY and POMC mRNAs expression in the hypothalamus; (3) orexin A upregulated LH and FSH mRNAs expression (FSH, P〉 0.05), but downregulated ghrelin mRNA expression in the pituitary. No significant effects were observed on the pituitary expression of FSH and POMC mRNAs. Our data suggest that orexin A regulates reproductive function by stimulating GnRH and LH release directly and indirectly via its effects on NPY, POMC and ghrelin expression.展开更多
Stress is an inevitable interference factor that seriously affects health.Listening to music is an economical,noninvasive,and highly accepted tool for easing stress.However,physiological studies investigating the abil...Stress is an inevitable interference factor that seriously affects health.Listening to music is an economical,noninvasive,and highly accepted tool for easing stress.However,physiological studies investigating the ability of music to reduce stress in daily life are limited.We established rat models of chronic immobilization stress(CIS)to observe changes in the hypothalamic arcuate nucleus(ARC)neurons involved in the regulation of food intake and the effect of comfortable classical music exposure.Twenty-one days of stress resulted in decreased food intake and delayed body weight gain,up-regulation of leptin receptor(Ob-R),cocaine-and amphetamine-regulated transcript(CART),proopiomelanocortin(POMC),and alpha-melanocyte-stimulating hormone(α-MSH)expression,and downregulation of neuropeptide Y(NPY)and agouti-related protein(AgRP)expression in the ARC.Thus,peripheral leptin entered the ARC under chronic stress conditions,bound to Ob-R,and affected downstream nerve pathways related to appetite,such as the NPY/AgRP and CART/POMC pathways.Gentle classical music played at 65 dB reversed the abnormal expression of Ob-R and NPY induced by chronic stress.Thus,listening to comfortable music improves changes in ARC neurons related to the regulation of food intake in CIS rats,and these results provide a reference for basic research regarding how music therapy alleviates stress and stress-related health issues.展开更多
In the present study, zooblooting, ELISA, and whole-mount immunocytochemistry methods were used to identify the FXPRLamide family neuropeptides from the Japanese oak silkworm, Antheraea yamamai. The results showed tha...In the present study, zooblooting, ELISA, and whole-mount immunocytochemistry methods were used to identify the FXPRLamide family neuropeptides from the Japanese oak silkworm, Antheraea yamamai. The results showed that the genomic DNA from A. yamamai showed positive bands after being hybridized with the fragment of DH-PBAN cDNA from Samia cynthia ricini, which was labeled with [α-32p]-dCTP. The SG showed highest FXPRLamide peptides titer in neural organs. Using an antiserum against Helicoverpa armigera PBAN, PBAN-like immunoreactivity was detected in the SG and TG of A. yamamai by whole-mount immunocytochemistry, and there were three cluster cells in the SG which shows positive PBAN-like immunoreactivity. The titers of FXPRLamide peptides immunoreactivity in the hemolymph were kept at a steady level. During pupation, the titer was increased promptly, but then decreased to a low level after the early pupal stage. The above-mentioned results demonstrate the existence of FXPRLamide family peptides in A. yamamai, but its function needs to be further investigated in the future.展开更多
Objective To investigate the effects and mechanism of calcitonin gene-related peptide(CGRP)and substance P (SP) on proliferation of rat bone marrow mesenchymal stem cells.Methods The rBMSCs were isolated using whole b...Objective To investigate the effects and mechanism of calcitonin gene-related peptide(CGRP)and substance P (SP) on proliferation of rat bone marrow mesenchymal stem cells.Methods The rBMSCs were isolated using whole bone marrow展开更多
The concentrations of central neuropeptides,somatostatin(SS) and substance-P (SP),were determined in the different brain regions of young-aged male rats after a long-term ad-m inistration of anticonvulsants Qingyangsh...The concentrations of central neuropeptides,somatostatin(SS) and substance-P (SP),were determined in the different brain regions of young-aged male rats after a long-term ad-m inistration of anticonvulsants Qingyangshen(QYS),Diphenylhydantoin(DPH),andCarbamazepine(CBZ).The results were compared with Pentylenetetrazol(PTZ)-inducedseizure model and normal saline-treated controls.No effects of QYS on the concentrationsof SS and SP were found in the rats of four-week or eight week groups.Both of DPH andPTZ increased the SS levels in the midbrain of rats in four-week gronp.DPH,CBZ,andPTZ also increased the SP levels in the cerebral cortex,striatum,and brain stem of rats ineight-week group.Our present data indicated that the central neuropeptides SS and SPwere involved in the processes of epilepsy and antiepilepsy.Since QYS did not influence thecontents of SS and SP after a long-term administration,it suggested that theanticonvulsant mechanism of QYS may be different from those of DPH and CBZ,i.e.itmay be not due to its effect on the central neuropeptide pathway.展开更多
Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexi- genic neuropeptides such as α-melatonin stimulating hormone (MS...Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexi- genic neuropeptides such as α-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expressions are up-regulated and POMC and CART gene ex- pressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mecha- nism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fasting increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in Y5-KO mice. RT-PCR and ISH suggested that the compensation of feeding is due to change in gene expressions of AgRP, CART and POMC in hypothalamus. Thus, these fi ndings indicated that the compensatory mechanism involves change in POMC/CART gene expression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.展开更多
Neuropeptides are crucial in regulation of a rich variety of developmental,physiological,and behavioral functions throughout the life cycle of insects.Using an integrated approach of multiomics,we identified neuropept...Neuropeptides are crucial in regulation of a rich variety of developmental,physiological,and behavioral functions throughout the life cycle of insects.Using an integrated approach of multiomics,we identified neuropeptide precursors in the greater wax moth Galleria mellonella,which is a harmful pest of honeybee hives with a worldwide distribution.Here,a total of 63 and 67 neuropeptide precursors were predicted and annotated in the G.mellonella genome and transcriptome,in which 40 neuropeptide precursors were confirmed in the G.mellonella peptidome.Interestingly,we identified 12 neuropeptide precursor genes present in G.mellonella but absent in honeybees,which may be potential novel pesticide target sites.Honeybee hives were contaminated with heavy metals such as lead,enabling its bioaccumulation in G.mellonella bodies through the food chain,we performed transcriptome sequencing to analyze the effects of Pb stress on the mRNA expression level of G.mellonella neuropeptide precursors.After treatment by Pb,the expression of neuropeptide F1 was found to be significantly downregulated,implying that this neuropeptide might be associated with responding to the heavy metal stress in G.mellonella.This study comprehensively identified neuropeptide precursors in G.mellonella,and discussed the effects of heavy metals on insect neuropeptides,with the example of G.mellonella.The results are valuable for future elucidation of how neuropeptides regulate physiological functions in G.mellonella and contribute to our understanding of the insect's environmental plasticity and identify potential new biomarkers to assess heavy metal toxicity in insects.展开更多
Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance.New devices are developing to increase the reliability of electrical skin impeda...Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance.New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness,skin thickness,size of the sensing electrode,pressure applied on the electrode,interelectrode distance,room temperature,and humidity.Morphological studies have identified that blood vessels,hair follicles,and nervous components are enhanced in the meridians/acupoints,which represent areas of potentially high neuronal activity.Recent evidence shows that nitric oxide(NO)concentrations are enhanced in skin acupoints/meridians.L-arginine-derived NO synthesis modifies skin norepinephrine(NE)synthesis/release in acupoints/meridians,and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation.NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1.Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area.Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints.Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field,the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components,and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints.The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system,which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.展开更多
Burying beetles (Nicrophorus sp.) are necrophagous insects with developed parental care. Genome of Nicrophorus vespilloides has been recently sequenced, which makes them interesting model organism in behavioral ecolog...Burying beetles (Nicrophorus sp.) are necrophagous insects with developed parental care. Genome of Nicrophorus vespilloides has been recently sequenced, which makes them interesting model organism in behavioral ecology. However, we know very little about their physiology, including the functioning of their neuroendocrine system. In this study, one of the physiological activities of proctolin, myosuppressin (Nieve? MS), myoinhibitory peptide (Trica-MIP-5) and the short neuropeptide F (Nicve-sNPF) in N. vespilloides have been investigated. The tested neuropeptides were myoactive on N. vespilloides hindgut. After application of the proctolin increased hindgut contraction frequency was observed (EC50 value was 5.47 x 10-8 mol/L). The other tested neuropeptides led to inhibition of N. vespilloides hindgut contractions (Nicve-MS: IC50 = 5.20 x 10~5 mol/L;Trica-MIP-5: IC50 = 5.95 x 10-6 mol/L;Nicvc-sNPF: IC50 = 4.08 x 10-5 mol/L). Moreover, the tested neuropeptides were immunolocalized in the nervous system of N. vespilloides. Neurons containing sNPF and MIP in brain and ventral nerve cord (VNC) were identified. Proctolin-immunolabeled neurons only in VNC were observed. Moreover, MIP-immunolabeled varicosities and fibers in retrocerebral complex were observed. In addition, our results have been supplemented with alignments of amino acid sequences of these neuropeptides in beetle species. This alignment analysis clearly showed amino acid sequence similarities between neuropeptides. Moreover, this allowed to deduce amino acid sequence of N. vespilloides proctolin (RYLPTa), Nicve-MS (QDVDHVFLRFa) and six isoforms ofNicve-MIP (Nicve-MIP-1一 DWNRNLHSWa;Nicve-MIP-2—AWQNLQGGWa;Nicve-MIP-3—AWQNLQGGWa;Nicve-MlP-4—AWKNLNNAGWa;Nicve-MIP-5—SEWGNFRGSWa;Nicve-MIP-6— DPAWTNLKGIWa;and Nicve-sNPF—SGRSPSLRLRFa).展开更多
Neuropeptides are widely distributed in vertebrates and invertebrates,regulating a variety of physiological activities in the organisms,such as metabolism,feeding and reproduction.In this study,to explore the function...Neuropeptides are widely distributed in vertebrates and invertebrates,regulating a variety of physiological activities in the organisms,such as metabolism,feeding and reproduction.In this study,to explore the function of neuropeptide LFRFamide in Sepia pharaonis,the full-length cDNA of LFRFamide-like gene(named SpLFRFL,MG869822.1)was identified with rapid amplification of cDNA ends(RACE)method.The sequence of SpLFRFL was 860 bp in length and encoded 188 amino acids containing 4 different mature peptides:1 copy of PHTPFRFamide,NSLFRFamide,TIFRFamide,and 3 copies of GNLFRFamide.Multiple alignment and phylogenetic analysis results showed that SpLFRFL shared high identity with LFRFamides of Sepia officinalis and Sepiella japonica and had the closest relationship with them.Through quantitative Real-time PCR(qRT-PCR),it was found that the SpLFRFL gene was highly expressed in the optic lobe and brain at three different stages during gonad development in both genders.Moreover,the four mature peptides at a concentration of 0.01μmol L^(−1) could inhibit the protein synthesis in the Chinese hamster ovary cell strain-K1(CHOK1)induced by SpGnRH.These data suggest that SpLFRFL might be involved in the development and reproduction of S.pharaonis.The results can contribute to future studies on neuropeptide evolution and function and benefit the cuttlefish farming.展开更多
Neuropeptides and their receptors are involved in the regulation and coordination of various physiological processes in insects.Although various neuropeptides have been identified previously,the corresponding receptor...Neuropeptides and their receptors are involved in the regulation and coordination of various physiological processes in insects.Although various neuropeptides have been identified previously,the corresponding receptors remain unknown in the oriental fruit fly,Bactrocera dorsalis,an important agricultural insect pest.It is also unclear whether neuropeptide signaling systems are involved in regulating the thermal tolerance of this notorious pest.Here,we systematically identified 44 putative neuropeptide receptor genes which encode 66 protein sequences,and analyzed the spatio-temporal expression patterns of the neuropeptide ligands and their receptor genes in B.dorsalis.We also analyzed changes in their transcript accumulation in two thermo-tolerant populations(heat and cold)of B.dorsalis.The results showed that numerous neuropeptides and receptors participate in responding to thermal stresses during acclimation.In particular,the expression of short neuropeptide F(sNPF)was up-regulated in the heat-tolerant population of B.dorsalis.Moreover,proteomic data showed that sNPF was up-regulated in both thermo-tolerant populations of B.dorsalis.The functional verification based on CRISPR/Cas9 demonstrated that sNPF is involved in regulating the tolerance to thermal stresses.The results of this study enrich our knowledge on the function of neuropeptide sNPF in insects.Moreover,this study demonstrated the role of neuropeptide signaling systems in thermal adaptation,contributing to a better understanding of the rapid invasiveness of B.dorsalis around the world.展开更多
Insect neuropeptides play an important role in regulating physiological functions such as growth,development,behavior and reproduction.We identified temperaturesensitive neuropeptides and receptor genes of the cotton ...Insect neuropeptides play an important role in regulating physiological functions such as growth,development,behavior and reproduction.We identified temperaturesensitive neuropeptides and receptor genes of the cotton whitefly,Bemisia tabaci.We identified 38 neuropeptide precursor genes and 35 neuropeptide receptors and constructed a phylogenetic tree using additional data from other insects.As temperature adaptability enables B.tabaci to colonize a diversity of habitats,we performed quantitative polymerase chain reaction with two temperature stresses(low=4℃ and high=40℃)to screen for temperature-sensitive neuropeptides.We found many neuropeptides and receptors that may be involved in the temperature adaptability of B.tabaci.This study is the first to identify B.tabaci neuropeptides and their receptors,and it will help to reveal the roles of neuropeptides in temperature adaptation of B.tabaci.展开更多
Substance P (SP) and vasoactive intestinal peptide (VIP) are neuropeptides synthesized in the dorsal root ganglion (DRG). These neuropeptides diffuse toward the central nervous system and peripheral nerve endings. It ...Substance P (SP) and vasoactive intestinal peptide (VIP) are neuropeptides synthesized in the dorsal root ganglion (DRG). These neuropeptides diffuse toward the central nervous system and peripheral nerve endings. It is now recognized that almost all the SP-containing DRG cells are small-sized (type B), accounting for 20% of total DRG cell population. SP is thought to be neurotransmitters involved in noxious information transmission for primary sensory afferent fibers, while VIP is also involved in sensory modulation. DRG is defined by Sherrington as the 'Laterally Located Brain', and recently is also called The Brain of Spinal Motion Segment and The Mediator of Low Back Pain. Much attention展开更多
Objective To examine the effect of neuropeptide Y (NPY) on TGF-β1 production in RAW264.7 macrophages. Methods Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 production. Cell counting kit 8 ...Objective To examine the effect of neuropeptide Y (NPY) on TGF-β1 production in RAW264.7 macrophages. Methods Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 production. Cell counting kit 8 (CCK-8) was used to assay the viability of RAW264.7 cells. Western blot was used to detect the phosphorylation of PI3K p85. Results NPY treatment could promote TGF-β1 production and rapid phosphorylation of PI3K p85 in RAW264.7 cells via Y1 receptor. The elevated TGF-β 1 production induced by NPY could be abolished by wortrnannin pretreatment. Conclusion NPY may elicit TGF-β production in RAW264.7 cells via Y1 receptor, and the activated PI3K pathway may account for this effect.展开更多
Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyper...Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.展开更多
Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases. Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The develo...Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases. Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The developing mechanisms, and the therapeutic tools of these diseases are still undefined. Several studies demonstrate that many hormones, neuropeptides and neurotransmitters regulate malignant and non-malignant cholangiocyte pathophysiology in the course of chronic biliary diseases. The aim of this review is to present the findings of several studies published in the recent years that contributed to clarifying the role of nervous and neuroendocrine regulation of the pathophysiologic events associated with cholestasis and cholangiocarcinoma development. This manuscript is organized into two parts. The first part offers an overview of the innervation of the liver and the origin of neuroendocrine hormones, neurotransmitters and neuropeptides affecting cholangiocyte function and metabolism. The first section also reviews the effects played by several neuroendocrine hormones and nervous system on cholangiocyte growth, survival and functional activity in the course of cholestasis. In the second section, we summarize the results of some studies describing the role of nervous system and neuroendocrine hormones in the regulation of malignant cholangiocyte growth.展开更多
The neuropeptides, substance P and calcitonin gene-related peptide, have been shown to be involved in pain transmission and repair of sciatic nerve injury. A model of sciatic nerve defect was prepared by dissecting th...The neuropeptides, substance P and calcitonin gene-related peptide, have been shown to be involved in pain transmission and repair of sciatic nerve injury. A model of sciatic nerve defect was prepared by dissecting the sciatic nerve at the middle, left femur in female Sprague Dawley rats. The two ends of the nerve were encased in a silica gel tube. L5 dorsal root ganglia were harvested 7, 14 and 28 days post sciatic nerve injury for immunohistochemical staining. Results showed that substance P and cal- citonin gene-related peptide expression increased significantly in dorsal root ganglion of rats with sci- atic nerve injury. This increase peaked at 7 days, declined at 14 days, and reduced to normal levels by 28 days post injury. The findings indicate that the neuropeptides, substance P and calcitonin gene- related peptide, mainly increased in the early stages after sciatic nerve injury.展开更多
Bombesin and neurotensin are neuropeptides which exert a wide spectrum of biological actions on gastrointestinal tissues influencing intestinal growth and adaptation, intestinal motility, blood flow, secretion, nutrie...Bombesin and neurotensin are neuropeptides which exert a wide spectrum of biological actions on gastrointestinal tissues influencing intestinal growth and adaptation, intestinal motility, blood flow, secretion, nutrient absorption and immune response. Based mainly on their well-established potent enterotrophic effect, numerous experimental studies investigated their potential positive effect on the atrophic or injured intestinal mucosa. These peptides proved to be effective mucosa-healing factors, but the potential molecular and cellular mechanisms for this action remained unresolved. In a recently published study (World J Gastroenterol 2008; 14(8): 1222-1230), it was shown that their protective effect on the intestine in experimentally induced inflammatory bowel disease was related to anti-inflammatory, antioxidant and antiapoptotic actions. These results are in close agreement with our previous studies on jaundiced and hepatectomized rats that showed a regulatory effect of bombesin and neurotensin on critical cellular processes such as enterocyte' proliferation and death, oxidative stress and redox equilibrium, tight junctions' formation and function, and inflammatory response. The pleiotropic effects of bombesin and neurotensin on diverse types of intestinal injury may justify their consideration for clinical trials.展开更多
文摘T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.
基金sponsored by the National Natural Sci-ence Foundation of China (30471248)
文摘Orexin has several biological functions, including the regulation of reproductive endocrine signaling, which has received much attention. However, little is known about the mechanism through which orexin regulates the levels of neuroendocrine hormones and peptides. We injected orexin A or physiological saline into the lateral ventricle of 10 ovariectomized (OVX) gilts, and determined the subsequent changes in serum luteinizing hormone (LH) concentration by using radioimmunoassay (RIA). We also examined the expression of GnRH, NPY, and POMC mRNAs in the hypothalamus and that of LH, folliclestimulating hormone (FSH), POMC, and ghrelin mRNAs in the pituitary by using semi-quantitative reverse transcription polymerase chain reaction. We found the following results: (1) Orexin A transiently promoted LH secretion; serum LH concentration started to increase at 10 min after the orexin injection, peaked at 30 min, and returned to its initial level at 1.5 h; (2) orexin A upregulated GnRH mRNA expression and downregulated NPY and POMC mRNAs expression in the hypothalamus; (3) orexin A upregulated LH and FSH mRNAs expression (FSH, P〉 0.05), but downregulated ghrelin mRNA expression in the pituitary. No significant effects were observed on the pituitary expression of FSH and POMC mRNAs. Our data suggest that orexin A regulates reproductive function by stimulating GnRH and LH release directly and indirectly via its effects on NPY, POMC and ghrelin expression.
基金the National Natural Science Foundation of China(No.81673881 and No.81202644)the Natural Science Foundation of Hebei Province(No.H2016423049)the Scientific Research Project of Hebei Administration of Traditional Chinese Medicine(No.2020045).
文摘Stress is an inevitable interference factor that seriously affects health.Listening to music is an economical,noninvasive,and highly accepted tool for easing stress.However,physiological studies investigating the ability of music to reduce stress in daily life are limited.We established rat models of chronic immobilization stress(CIS)to observe changes in the hypothalamic arcuate nucleus(ARC)neurons involved in the regulation of food intake and the effect of comfortable classical music exposure.Twenty-one days of stress resulted in decreased food intake and delayed body weight gain,up-regulation of leptin receptor(Ob-R),cocaine-and amphetamine-regulated transcript(CART),proopiomelanocortin(POMC),and alpha-melanocyte-stimulating hormone(α-MSH)expression,and downregulation of neuropeptide Y(NPY)and agouti-related protein(AgRP)expression in the ARC.Thus,peripheral leptin entered the ARC under chronic stress conditions,bound to Ob-R,and affected downstream nerve pathways related to appetite,such as the NPY/AgRP and CART/POMC pathways.Gentle classical music played at 65 dB reversed the abnormal expression of Ob-R and NPY induced by chronic stress.Thus,listening to comfortable music improves changes in ARC neurons related to the regulation of food intake in CIS rats,and these results provide a reference for basic research regarding how music therapy alleviates stress and stress-related health issues.
基金Acknowledgements This study was supported by a Grant-in-Aid for the Natural Scientific Foundation (30500374) from the National Natural Science Foundation of China, the Key Research Program of Anhui Province, China (05021003).
文摘In the present study, zooblooting, ELISA, and whole-mount immunocytochemistry methods were used to identify the FXPRLamide family neuropeptides from the Japanese oak silkworm, Antheraea yamamai. The results showed that the genomic DNA from A. yamamai showed positive bands after being hybridized with the fragment of DH-PBAN cDNA from Samia cynthia ricini, which was labeled with [α-32p]-dCTP. The SG showed highest FXPRLamide peptides titer in neural organs. Using an antiserum against Helicoverpa armigera PBAN, PBAN-like immunoreactivity was detected in the SG and TG of A. yamamai by whole-mount immunocytochemistry, and there were three cluster cells in the SG which shows positive PBAN-like immunoreactivity. The titers of FXPRLamide peptides immunoreactivity in the hemolymph were kept at a steady level. During pupation, the titer was increased promptly, but then decreased to a low level after the early pupal stage. The above-mentioned results demonstrate the existence of FXPRLamide family peptides in A. yamamai, but its function needs to be further investigated in the future.
文摘Objective To investigate the effects and mechanism of calcitonin gene-related peptide(CGRP)and substance P (SP) on proliferation of rat bone marrow mesenchymal stem cells.Methods The rBMSCs were isolated using whole bone marrow
文摘The concentrations of central neuropeptides,somatostatin(SS) and substance-P (SP),were determined in the different brain regions of young-aged male rats after a long-term ad-m inistration of anticonvulsants Qingyangshen(QYS),Diphenylhydantoin(DPH),andCarbamazepine(CBZ).The results were compared with Pentylenetetrazol(PTZ)-inducedseizure model and normal saline-treated controls.No effects of QYS on the concentrationsof SS and SP were found in the rats of four-week or eight week groups.Both of DPH andPTZ increased the SS levels in the midbrain of rats in four-week gronp.DPH,CBZ,andPTZ also increased the SP levels in the cerebral cortex,striatum,and brain stem of rats ineight-week group.Our present data indicated that the central neuropeptides SS and SPwere involved in the processes of epilepsy and antiepilepsy.Since QYS did not influence thecontents of SS and SP after a long-term administration,it suggested that theanticonvulsant mechanism of QYS may be different from those of DPH and CBZ,i.e.itmay be not due to its effect on the central neuropeptide pathway.
文摘Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexi- genic neuropeptides such as α-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expressions are up-regulated and POMC and CART gene ex- pressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mecha- nism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fasting increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in Y5-KO mice. RT-PCR and ISH suggested that the compensation of feeding is due to change in gene expressions of AgRP, CART and POMC in hypothalamus. Thus, these fi ndings indicated that the compensatory mechanism involves change in POMC/CART gene expression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.
基金supported in part by the National Natural Science Foundation of China(32202295)Guizhou Provincial Science and Technology Projects(Qian Ke He Ji Chu-ZK[2022]General 051)+1 种基金Scientific Research Foundation for Talent Introduced in Guizhou University(Gui Da Te Gang He Zi[2021]22)Guizhou Provincial Science and Technology Projects(Qian Ke He Support[2019]2292,Qian Ke He NY[2013]3040).
文摘Neuropeptides are crucial in regulation of a rich variety of developmental,physiological,and behavioral functions throughout the life cycle of insects.Using an integrated approach of multiomics,we identified neuropeptide precursors in the greater wax moth Galleria mellonella,which is a harmful pest of honeybee hives with a worldwide distribution.Here,a total of 63 and 67 neuropeptide precursors were predicted and annotated in the G.mellonella genome and transcriptome,in which 40 neuropeptide precursors were confirmed in the G.mellonella peptidome.Interestingly,we identified 12 neuropeptide precursor genes present in G.mellonella but absent in honeybees,which may be potential novel pesticide target sites.Honeybee hives were contaminated with heavy metals such as lead,enabling its bioaccumulation in G.mellonella bodies through the food chain,we performed transcriptome sequencing to analyze the effects of Pb stress on the mRNA expression level of G.mellonella neuropeptide precursors.After treatment by Pb,the expression of neuropeptide F1 was found to be significantly downregulated,implying that this neuropeptide might be associated with responding to the heavy metal stress in G.mellonella.This study comprehensively identified neuropeptide precursors in G.mellonella,and discussed the effects of heavy metals on insect neuropeptides,with the example of G.mellonella.The results are valuable for future elucidation of how neuropeptides regulate physiological functions in G.mellonella and contribute to our understanding of the insect's environmental plasticity and identify potential new biomarkers to assess heavy metal toxicity in insects.
基金Supported by NIH Grant(No.AT002478,AT004620,and AT004504)from the National Center for Complementary and Integrative Health。
文摘Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance.New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness,skin thickness,size of the sensing electrode,pressure applied on the electrode,interelectrode distance,room temperature,and humidity.Morphological studies have identified that blood vessels,hair follicles,and nervous components are enhanced in the meridians/acupoints,which represent areas of potentially high neuronal activity.Recent evidence shows that nitric oxide(NO)concentrations are enhanced in skin acupoints/meridians.L-arginine-derived NO synthesis modifies skin norepinephrine(NE)synthesis/release in acupoints/meridians,and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation.NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1.Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area.Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints.Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field,the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components,and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints.The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system,which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.
文摘Burying beetles (Nicrophorus sp.) are necrophagous insects with developed parental care. Genome of Nicrophorus vespilloides has been recently sequenced, which makes them interesting model organism in behavioral ecology. However, we know very little about their physiology, including the functioning of their neuroendocrine system. In this study, one of the physiological activities of proctolin, myosuppressin (Nieve? MS), myoinhibitory peptide (Trica-MIP-5) and the short neuropeptide F (Nicve-sNPF) in N. vespilloides have been investigated. The tested neuropeptides were myoactive on N. vespilloides hindgut. After application of the proctolin increased hindgut contraction frequency was observed (EC50 value was 5.47 x 10-8 mol/L). The other tested neuropeptides led to inhibition of N. vespilloides hindgut contractions (Nicve-MS: IC50 = 5.20 x 10~5 mol/L;Trica-MIP-5: IC50 = 5.95 x 10-6 mol/L;Nicvc-sNPF: IC50 = 4.08 x 10-5 mol/L). Moreover, the tested neuropeptides were immunolocalized in the nervous system of N. vespilloides. Neurons containing sNPF and MIP in brain and ventral nerve cord (VNC) were identified. Proctolin-immunolabeled neurons only in VNC were observed. Moreover, MIP-immunolabeled varicosities and fibers in retrocerebral complex were observed. In addition, our results have been supplemented with alignments of amino acid sequences of these neuropeptides in beetle species. This alignment analysis clearly showed amino acid sequence similarities between neuropeptides. Moreover, this allowed to deduce amino acid sequence of N. vespilloides proctolin (RYLPTa), Nicve-MS (QDVDHVFLRFa) and six isoforms ofNicve-MIP (Nicve-MIP-1一 DWNRNLHSWa;Nicve-MIP-2—AWQNLQGGWa;Nicve-MIP-3—AWQNLQGGWa;Nicve-MlP-4—AWKNLNNAGWa;Nicve-MIP-5—SEWGNFRGSWa;Nicve-MIP-6— DPAWTNLKGIWa;and Nicve-sNPF—SGRSPSLRLRFa).
基金supported by the National Natural Science Foundation of China(No.31872547)the Natural Science Foundation of Zhejiang Province,China(No.LY20 C190007)+1 种基金the Open Foundation from Marine Sciences in the First-Class Subjects of Zhejiang(No.OFMS004)the Excellent Postdoctoral Program of Jiangsu Province(No.314865).
文摘Neuropeptides are widely distributed in vertebrates and invertebrates,regulating a variety of physiological activities in the organisms,such as metabolism,feeding and reproduction.In this study,to explore the function of neuropeptide LFRFamide in Sepia pharaonis,the full-length cDNA of LFRFamide-like gene(named SpLFRFL,MG869822.1)was identified with rapid amplification of cDNA ends(RACE)method.The sequence of SpLFRFL was 860 bp in length and encoded 188 amino acids containing 4 different mature peptides:1 copy of PHTPFRFamide,NSLFRFamide,TIFRFamide,and 3 copies of GNLFRFamide.Multiple alignment and phylogenetic analysis results showed that SpLFRFL shared high identity with LFRFamides of Sepia officinalis and Sepiella japonica and had the closest relationship with them.Through quantitative Real-time PCR(qRT-PCR),it was found that the SpLFRFL gene was highly expressed in the optic lobe and brain at three different stages during gonad development in both genders.Moreover,the four mature peptides at a concentration of 0.01μmol L^(−1) could inhibit the protein synthesis in the Chinese hamster ovary cell strain-K1(CHOK1)induced by SpGnRH.These data suggest that SpLFRFL might be involved in the development and reproduction of S.pharaonis.The results can contribute to future studies on neuropeptide evolution and function and benefit the cuttlefish farming.
基金supported by funding from the National Natural Science Foundation of China(U21A20222 and 32072491)the National Key R&D Program of China(2022YFC2601000)the 111 Project,China(B18044)and the earmarked fund for China Agriculture Research System(CARS-26)。
文摘Neuropeptides and their receptors are involved in the regulation and coordination of various physiological processes in insects.Although various neuropeptides have been identified previously,the corresponding receptors remain unknown in the oriental fruit fly,Bactrocera dorsalis,an important agricultural insect pest.It is also unclear whether neuropeptide signaling systems are involved in regulating the thermal tolerance of this notorious pest.Here,we systematically identified 44 putative neuropeptide receptor genes which encode 66 protein sequences,and analyzed the spatio-temporal expression patterns of the neuropeptide ligands and their receptor genes in B.dorsalis.We also analyzed changes in their transcript accumulation in two thermo-tolerant populations(heat and cold)of B.dorsalis.The results showed that numerous neuropeptides and receptors participate in responding to thermal stresses during acclimation.In particular,the expression of short neuropeptide F(sNPF)was up-regulated in the heat-tolerant population of B.dorsalis.Moreover,proteomic data showed that sNPF was up-regulated in both thermo-tolerant populations of B.dorsalis.The functional verification based on CRISPR/Cas9 demonstrated that sNPF is involved in regulating the tolerance to thermal stresses.The results of this study enrich our knowledge on the function of neuropeptide sNPF in insects.Moreover,this study demonstrated the role of neuropeptide signaling systems in thermal adaptation,contributing to a better understanding of the rapid invasiveness of B.dorsalis around the world.
基金the Qingdao Agricultural University Highlevel Talent Fund(665-1117002663-1119002)+1 种基金Qingdao Agricultural University Graduate Innovation Program(QYC201809)the National Nature Science Foundation of China(31901948).
文摘Insect neuropeptides play an important role in regulating physiological functions such as growth,development,behavior and reproduction.We identified temperaturesensitive neuropeptides and receptor genes of the cotton whitefly,Bemisia tabaci.We identified 38 neuropeptide precursor genes and 35 neuropeptide receptors and constructed a phylogenetic tree using additional data from other insects.As temperature adaptability enables B.tabaci to colonize a diversity of habitats,we performed quantitative polymerase chain reaction with two temperature stresses(low=4℃ and high=40℃)to screen for temperature-sensitive neuropeptides.We found many neuropeptides and receptors that may be involved in the temperature adaptability of B.tabaci.This study is the first to identify B.tabaci neuropeptides and their receptors,and it will help to reveal the roles of neuropeptides in temperature adaptation of B.tabaci.
文摘Substance P (SP) and vasoactive intestinal peptide (VIP) are neuropeptides synthesized in the dorsal root ganglion (DRG). These neuropeptides diffuse toward the central nervous system and peripheral nerve endings. It is now recognized that almost all the SP-containing DRG cells are small-sized (type B), accounting for 20% of total DRG cell population. SP is thought to be neurotransmitters involved in noxious information transmission for primary sensory afferent fibers, while VIP is also involved in sensory modulation. DRG is defined by Sherrington as the 'Laterally Located Brain', and recently is also called The Brain of Spinal Motion Segment and The Mediator of Low Back Pain. Much attention
文摘Objective To examine the effect of neuropeptide Y (NPY) on TGF-β1 production in RAW264.7 macrophages. Methods Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 production. Cell counting kit 8 (CCK-8) was used to assay the viability of RAW264.7 cells. Western blot was used to detect the phosphorylation of PI3K p85. Results NPY treatment could promote TGF-β1 production and rapid phosphorylation of PI3K p85 in RAW264.7 cells via Y1 receptor. The elevated TGF-β 1 production induced by NPY could be abolished by wortrnannin pretreatment. Conclusion NPY may elicit TGF-β production in RAW264.7 cells via Y1 receptor, and the activated PI3K pathway may account for this effect.
基金Supported by Grants from the Ministerio de Cienciae Innovacion,No.SAF2009-07408CIBER de Diabetesy Enfermedades Metabólicas Asociadas and Generaltitat de Catalunya,No. 2009SGR739
文摘Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.
基金the MIUR grant, No. 2003060137_004 and by the Fondazione Cariverona 2002 grant "Ambienre e sviluppo sostenibile" to Prof. Benedetti by the "Premio S.I.G.E. 2004" to Dr. Marzioni by the Universita Politecnica delle Marche intramural grants ATBEN00205 to Professor. Benedetti and ATMAROl 105 to Dr. Marzioni, by the "Premio S.I.G.E. 2006" to Dr Fava
文摘Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases. Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The developing mechanisms, and the therapeutic tools of these diseases are still undefined. Several studies demonstrate that many hormones, neuropeptides and neurotransmitters regulate malignant and non-malignant cholangiocyte pathophysiology in the course of chronic biliary diseases. The aim of this review is to present the findings of several studies published in the recent years that contributed to clarifying the role of nervous and neuroendocrine regulation of the pathophysiologic events associated with cholestasis and cholangiocarcinoma development. This manuscript is organized into two parts. The first part offers an overview of the innervation of the liver and the origin of neuroendocrine hormones, neurotransmitters and neuropeptides affecting cholangiocyte function and metabolism. The first section also reviews the effects played by several neuroendocrine hormones and nervous system on cholangiocyte growth, survival and functional activity in the course of cholestasis. In the second section, we summarize the results of some studies describing the role of nervous system and neuroendocrine hormones in the regulation of malignant cholangiocyte growth.
基金supported by the Major Program of Science and Technology of Ministry of Education,No.207049
文摘The neuropeptides, substance P and calcitonin gene-related peptide, have been shown to be involved in pain transmission and repair of sciatic nerve injury. A model of sciatic nerve defect was prepared by dissecting the sciatic nerve at the middle, left femur in female Sprague Dawley rats. The two ends of the nerve were encased in a silica gel tube. L5 dorsal root ganglia were harvested 7, 14 and 28 days post sciatic nerve injury for immunohistochemical staining. Results showed that substance P and cal- citonin gene-related peptide expression increased significantly in dorsal root ganglion of rats with sci- atic nerve injury. This increase peaked at 7 days, declined at 14 days, and reduced to normal levels by 28 days post injury. The findings indicate that the neuropeptides, substance P and calcitonin gene- related peptide, mainly increased in the early stages after sciatic nerve injury.
文摘Bombesin and neurotensin are neuropeptides which exert a wide spectrum of biological actions on gastrointestinal tissues influencing intestinal growth and adaptation, intestinal motility, blood flow, secretion, nutrient absorption and immune response. Based mainly on their well-established potent enterotrophic effect, numerous experimental studies investigated their potential positive effect on the atrophic or injured intestinal mucosa. These peptides proved to be effective mucosa-healing factors, but the potential molecular and cellular mechanisms for this action remained unresolved. In a recently published study (World J Gastroenterol 2008; 14(8): 1222-1230), it was shown that their protective effect on the intestine in experimentally induced inflammatory bowel disease was related to anti-inflammatory, antioxidant and antiapoptotic actions. These results are in close agreement with our previous studies on jaundiced and hepatectomized rats that showed a regulatory effect of bombesin and neurotensin on critical cellular processes such as enterocyte' proliferation and death, oxidative stress and redox equilibrium, tight junctions' formation and function, and inflammatory response. The pleiotropic effects of bombesin and neurotensin on diverse types of intestinal injury may justify their consideration for clinical trials.