Brain-derived neurotrophic factor(BDNF) plays an important role in central nervous system development, neurogenesis and neuronal plasticity. BDNF is also expressed in several non-neuronal tissues, and it could play an...Brain-derived neurotrophic factor(BDNF) plays an important role in central nervous system development, neurogenesis and neuronal plasticity. BDNF is also expressed in several non-neuronal tissues, and it could play an important role in other processes, such as cancer, angiogenesis, etc. Platelets are the major source of peripheral BDNF. However, platelets also contain high amounts of serotonin; they express specific surface receptors during activation, and a multitude of pro-inflammatory and immunomodulatory bioactive compounds are secreted from the granules. Until recently, there was insufficient knowledge regarding the relationship between BDNF and platelets. Recent studies showed that BDNF is present in two distinct pools in platelets, in α-granules and in the cytoplasm, and only the BDNF in the granules is secreted following stimulation, representing 30% of the total BDNF in platelets. BDNF has an important role in the pathophysiology of depression. Low levels of serum BDNF have been described in patients with major depressive disorder, and BDNF levels increased with chronic antidepressant treatment. Interestingly, there is an association between depression and platelet function. This review analyzed studies that evaluated the relationship between BDNF and platelet activation and the effect of treatments on both parameters. Only a few studies consider this possible confounding factor, and it could be very important in diseases such as depression, which show changes in both parameters.展开更多
Multiple Sclerosis(MS)is a chronic,inflammatory and degenerative disease of the central nervous system(CNS)with an unknown etiology.The MS pathophysiology is due to altered bidirectional interactions between several i...Multiple Sclerosis(MS)is a chronic,inflammatory and degenerative disease of the central nervous system(CNS)with an unknown etiology.The MS pathophysiology is due to altered bidirectional interactions between several immune cell types in the periphery(such as T and B cells,myeloid cells)and resident CNS cells(such as microglia and astrocytes).It is also known that inflammatory responses have both detrimental and neuroprotective effects.The release of brain derived neurotrophic factor(BDNF)by immune cells,in both peripheral blood and into inflammatory lesions in MS,but also by microglia and astrocytes,into the CNS,seems to be a possible mechanism for this neuroprotective effect.So far,the link between BDNF and neuroinflammation has been poorly investigated.A better understanding of this link could help in the development of new therapeutic strategies for MS.In this review,the role of BDNF in MS will be discussed as well as its possible alternative as an innovative therapeutic target.展开更多
Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes a rat auditory nerve (AN...Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes a rat auditory nerve (AN) directed transplantation of human neural progenitor cells (HNPCs) as a cell replacement therapy for impaired auditory function. Groups of b-bungarotoxin induced auditory function compromised female rats were used to transplant HNPCs in the nerve trunk. In the treatment groups, brain derived neurotrophic factor (BDNF), peptide amphiphile nanofiber bioactive gel (Bgel) and Chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core of chondroitin sulphate proteoglycans, were added along with HNPCs while the control groups were with PA inert gel (Igel) and devoid of ChABC. Six weeks post transplantation survival, migration, and differentiation of HNPCs were studied and compared. The groups treated with BDNF and Bgel showed improved survival and differentiation of transplanted HNPCs while the ChABC treated group showed significant migration of HNPCs along the AN and elongation of neuronal fibers along the nerve towards the cochlear nucleus (CN) which was characterized by immunocytochemical markers for human Nuclei (HuN), human mitochondria (HuM) and neuronal β-tubulin (Tuj1). These findings show that addition of BDNF and ChABC consisted Bgel environment facilitated HNPC survival, migration and differentiation along the transplanted rat AN towards the CN. This transplantation strategy provides unique experimental validation for futuristic role of cell based biomaterial consisted neurotrophic factor application in clinically transferable treatment of sensorineural hearing loss (SNHL) along with cochlear implants (CI).展开更多
This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related fact...This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway,anti-oxidative stress effects,enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway,increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway,and reducing the activity of the hypothalamic-pituitary-adrenocortical axis.We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning,shallow depth of stimulation,and difficulty in elucidating the neural circuit mechanism up-and down-stream of the stimulation target brain region.展开更多
A pathophysiological relationship has been reported between inflammatory processes,decreased levels of neurotrophins,increased oxidative stress and psychiatric disorders in both juvenile and adult ages.Moreover,this r...A pathophysiological relationship has been reported between inflammatory processes,decreased levels of neurotrophins,increased oxidative stress and psychiatric disorders in both juvenile and adult ages.Moreover,this relationship remains unclear in juvenile bipolar disorder(BD).We performed a systematic literature review of studies reporting measurements of inflammatory markers,oxidative stress markers or neurotrophins in juvenile and young adult subjects with BD.Concordant findings showed that inflammatory markers are increased since the earlier stages of BD.A positive correlation between decreased levels of a peripheral brain-derived neurotrophic factor and juvenile BD is controversial suggesting that those changes might occur only during the late stage of BD.No changes in central glutathione levels were reported in young adult age BD indicating that oxidative stress may be an outcome of long illness duration and repeated affective episodes.In conclusion,preliminary findings indicate that a certain relationship exists between inflammatory process and juvenile BD but evidence are insufficient to support a causal relationship.Adequately powered and prospective studies are warranted to clarify the role of inflammation,neurotrophins and oxidative stress in juvenile BD.展开更多
文摘Brain-derived neurotrophic factor(BDNF) plays an important role in central nervous system development, neurogenesis and neuronal plasticity. BDNF is also expressed in several non-neuronal tissues, and it could play an important role in other processes, such as cancer, angiogenesis, etc. Platelets are the major source of peripheral BDNF. However, platelets also contain high amounts of serotonin; they express specific surface receptors during activation, and a multitude of pro-inflammatory and immunomodulatory bioactive compounds are secreted from the granules. Until recently, there was insufficient knowledge regarding the relationship between BDNF and platelets. Recent studies showed that BDNF is present in two distinct pools in platelets, in α-granules and in the cytoplasm, and only the BDNF in the granules is secreted following stimulation, representing 30% of the total BDNF in platelets. BDNF has an important role in the pathophysiology of depression. Low levels of serum BDNF have been described in patients with major depressive disorder, and BDNF levels increased with chronic antidepressant treatment. Interestingly, there is an association between depression and platelet function. This review analyzed studies that evaluated the relationship between BDNF and platelet activation and the effect of treatments on both parameters. Only a few studies consider this possible confounding factor, and it could be very important in diseases such as depression, which show changes in both parameters.
文摘Multiple Sclerosis(MS)is a chronic,inflammatory and degenerative disease of the central nervous system(CNS)with an unknown etiology.The MS pathophysiology is due to altered bidirectional interactions between several immune cell types in the periphery(such as T and B cells,myeloid cells)and resident CNS cells(such as microglia and astrocytes).It is also known that inflammatory responses have both detrimental and neuroprotective effects.The release of brain derived neurotrophic factor(BDNF)by immune cells,in both peripheral blood and into inflammatory lesions in MS,but also by microglia and astrocytes,into the CNS,seems to be a possible mechanism for this neuroprotective effect.So far,the link between BDNF and neuroinflammation has been poorly investigated.A better understanding of this link could help in the development of new therapeutic strategies for MS.In this review,the role of BDNF in MS will be discussed as well as its possible alternative as an innovative therapeutic target.
基金supported by The Swedish Research Council no.2008-2822,Marianne and Marcus Wallenbergs Foundation,Petrus and Augusta Hedlunds Foundation,The Swedish Association of Hard of Hearing People,Acta Otolaryngologica’s Foundation,The Foundation Tysta Skolan,Ollie and Elof Ericssons Foundation for Medical Research and Karolinska Institutet Foundationssupported by the Medical faculty and Lund University.
文摘Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes a rat auditory nerve (AN) directed transplantation of human neural progenitor cells (HNPCs) as a cell replacement therapy for impaired auditory function. Groups of b-bungarotoxin induced auditory function compromised female rats were used to transplant HNPCs in the nerve trunk. In the treatment groups, brain derived neurotrophic factor (BDNF), peptide amphiphile nanofiber bioactive gel (Bgel) and Chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core of chondroitin sulphate proteoglycans, were added along with HNPCs while the control groups were with PA inert gel (Igel) and devoid of ChABC. Six weeks post transplantation survival, migration, and differentiation of HNPCs were studied and compared. The groups treated with BDNF and Bgel showed improved survival and differentiation of transplanted HNPCs while the ChABC treated group showed significant migration of HNPCs along the AN and elongation of neuronal fibers along the nerve towards the cochlear nucleus (CN) which was characterized by immunocytochemical markers for human Nuclei (HuN), human mitochondria (HuM) and neuronal β-tubulin (Tuj1). These findings show that addition of BDNF and ChABC consisted Bgel environment facilitated HNPC survival, migration and differentiation along the transplanted rat AN towards the CN. This transplantation strategy provides unique experimental validation for futuristic role of cell based biomaterial consisted neurotrophic factor application in clinically transferable treatment of sensorineural hearing loss (SNHL) along with cochlear implants (CI).
基金National Key R and D Program of China,No.2016YFC1306700The Key Projects of National Natural Science Foundation of China,No.81830040+1 种基金Science and Technology Program of Guangdong,China,No.2018B030334001Program of Excellent Talents in Medical Science of Jiangsu Province,China,No.JCRCA2016006.
文摘This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway,anti-oxidative stress effects,enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway,increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway,and reducing the activity of the hypothalamic-pituitary-adrenocortical axis.We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning,shallow depth of stimulation,and difficulty in elucidating the neural circuit mechanism up-and down-stream of the stimulation target brain region.
基金It was supported by the Research Fellowship from Sapienza University of Rome to Dr.Giulia Serra.
文摘A pathophysiological relationship has been reported between inflammatory processes,decreased levels of neurotrophins,increased oxidative stress and psychiatric disorders in both juvenile and adult ages.Moreover,this relationship remains unclear in juvenile bipolar disorder(BD).We performed a systematic literature review of studies reporting measurements of inflammatory markers,oxidative stress markers or neurotrophins in juvenile and young adult subjects with BD.Concordant findings showed that inflammatory markers are increased since the earlier stages of BD.A positive correlation between decreased levels of a peripheral brain-derived neurotrophic factor and juvenile BD is controversial suggesting that those changes might occur only during the late stage of BD.No changes in central glutathione levels were reported in young adult age BD indicating that oxidative stress may be an outcome of long illness duration and repeated affective episodes.In conclusion,preliminary findings indicate that a certain relationship exists between inflammatory process and juvenile BD but evidence are insufficient to support a causal relationship.Adequately powered and prospective studies are warranted to clarify the role of inflammation,neurotrophins and oxidative stress in juvenile BD.
