Neurotoxicity induced by stress,radiation,chemicals,or metabolic diseases,is commonly associated with excitotoxicity,oxidative stress,and neuroinflammation.The pathological process of neurotoxicity induces neuronal de...Neurotoxicity induced by stress,radiation,chemicals,or metabolic diseases,is commonly associated with excitotoxicity,oxidative stress,and neuroinflammation.The pathological process of neurotoxicity induces neuronal death,interrupts synaptic plasticity in the brain,and is similar to that of diverse neurodegenerative diseases.Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes.Specifically,brain-derived neurotropic factor（BDNF） and gamma-aminobutyric acid（GABA）-ergic transmission are related to both neurodegeneration and neuroregeneration.This review summarizes the accumulating evidences that suggest a pathogenic role of BDNF and GABAergic transmission,their underlying mechanisms,and the relationship between BDNF and GABA in neurodegeneration and neuroregeneration.This review will provide a comprehensive overview of the underlying mechanisms of neuroregeneration that may help in developing potential strategies for pharmacotherapeutic approaches to treat neurotoxicity and neurodegenerative disease.展开更多
A role of lower brain-derived neurotrophic factor (BDNF) content in the pathogenesis of several mental illnesses has been suggested, especially in major depression. It is not known whether BDNF is involved in the path...A role of lower brain-derived neurotrophic factor (BDNF) content in the pathogenesis of several mental illnesses has been suggested, especially in major depression. It is not known whether BDNF is involved in the pathogenesis of obsessive-compulsive disorder (OCD). Herein, we assessed the serum BDNF content and its correlation with symptom severity in a Japanese population with OCD. The serum BDNF levels of OCD patients (n = 39) and healthy controls (n = 37) were measured by ELISA. The severity of OCD symptoms was assessed by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Beck Depression Inventory (BDI). The OCD patients’ BDNF levels were significantly higher than those of the controls (17.5 ± 7.3 vs. 12.7 ± 4.7) (p < 0.01). No correlation was observed between the OCD patients’ BDNF levels and their OCD symptoms as scored by the Y-BOCS. For all 76 subjects, the BDI scores were significantly negatively correlated with the serum BDNF levels. Our findings revealed that contrary to previous reports, the serum BDNF content in OCD patients could be higher than that of healthy subjects.展开更多
Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits neuronal survival and differentiation, synaptic transmission, and the modulation of synaptic plasticity. The biological actions of BDNF are media...Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits neuronal survival and differentiation, synaptic transmission, and the modulation of synaptic plasticity. The biological actions of BDNF are mediated via two distinct receptors: the high-affinity tropomyosin-related kinase B (TrkB) receptor and the low-affinity p75 neurotrophin receptor (p75NTR). Recent findings regarding the actions and mechanisms of BDNF are reviewed here. Activity-dependent synaptic plasticity, as exemplified by long-term potentiation (LTP) and long-term depression (LTD), underlies the cellular mechanism of learning and memory. An accumulating body of evidence shows that BDNF modulates synaptic plasticity. This function requires extracellular neurotrophin release, synaptic activity-dependent local protein synthesis. In addition, a precursor of BDNF, proBDNF, is emerging as a new ligand with biological activities that are distinct from those of BDNF. The proteolytic cleavage of proBDNF is also proposed as a mechanism that determines the direction of BDNF actions. This review discusses the post-translational processing of proBDNF, the modulatory roles of the human BDNF polymorphism Val66Met, recent reports of the novel mechanisms of BDNF expression, and clinical reports showing the roles of BDNF in the blood. Taken together, these data provide new insights into the biological roles of BDNF and its related molecules in the central nervous system.展开更多
基金supported by a grant from Wonkwang University in 2017
文摘Neurotoxicity induced by stress,radiation,chemicals,or metabolic diseases,is commonly associated with excitotoxicity,oxidative stress,and neuroinflammation.The pathological process of neurotoxicity induces neuronal death,interrupts synaptic plasticity in the brain,and is similar to that of diverse neurodegenerative diseases.Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes.Specifically,brain-derived neurotropic factor（BDNF） and gamma-aminobutyric acid（GABA）-ergic transmission are related to both neurodegeneration and neuroregeneration.This review summarizes the accumulating evidences that suggest a pathogenic role of BDNF and GABAergic transmission,their underlying mechanisms,and the relationship between BDNF and GABA in neurodegeneration and neuroregeneration.This review will provide a comprehensive overview of the underlying mechanisms of neuroregeneration that may help in developing potential strategies for pharmacotherapeutic approaches to treat neurotoxicity and neurodegenerative disease.
文摘A role of lower brain-derived neurotrophic factor (BDNF) content in the pathogenesis of several mental illnesses has been suggested, especially in major depression. It is not known whether BDNF is involved in the pathogenesis of obsessive-compulsive disorder (OCD). Herein, we assessed the serum BDNF content and its correlation with symptom severity in a Japanese population with OCD. The serum BDNF levels of OCD patients (n = 39) and healthy controls (n = 37) were measured by ELISA. The severity of OCD symptoms was assessed by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Beck Depression Inventory (BDI). The OCD patients’ BDNF levels were significantly higher than those of the controls (17.5 ± 7.3 vs. 12.7 ± 4.7) (p < 0.01). No correlation was observed between the OCD patients’ BDNF levels and their OCD symptoms as scored by the Y-BOCS. For all 76 subjects, the BDI scores were significantly negatively correlated with the serum BDNF levels. Our findings revealed that contrary to previous reports, the serum BDNF content in OCD patients could be higher than that of healthy subjects.
文摘Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits neuronal survival and differentiation, synaptic transmission, and the modulation of synaptic plasticity. The biological actions of BDNF are mediated via two distinct receptors: the high-affinity tropomyosin-related kinase B (TrkB) receptor and the low-affinity p75 neurotrophin receptor (p75NTR). Recent findings regarding the actions and mechanisms of BDNF are reviewed here. Activity-dependent synaptic plasticity, as exemplified by long-term potentiation (LTP) and long-term depression (LTD), underlies the cellular mechanism of learning and memory. An accumulating body of evidence shows that BDNF modulates synaptic plasticity. This function requires extracellular neurotrophin release, synaptic activity-dependent local protein synthesis. In addition, a precursor of BDNF, proBDNF, is emerging as a new ligand with biological activities that are distinct from those of BDNF. The proteolytic cleavage of proBDNF is also proposed as a mechanism that determines the direction of BDNF actions. This review discusses the post-translational processing of proBDNF, the modulatory roles of the human BDNF polymorphism Val66Met, recent reports of the novel mechanisms of BDNF expression, and clinical reports showing the roles of BDNF in the blood. Taken together, these data provide new insights into the biological roles of BDNF and its related molecules in the central nervous system.
