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
Gadolinium (Gd3+) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd3+ ...Gadolinium (Gd3+) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd3+ on neurons in the complex central nervous system (CNS), the neurotoxic actions of GdCl3 have been investigated in both neuron monoculture and astrocyte-neuron co-culture systems. Measurements of lactate dehydrogenase release showed that GdCl3 causes significant cell death of monocultured neurons as a result of reactive oxygen species (ROS) generation and down-regulation of brain-derived neurotrophic factor (BDNF). However, GdCl3 does not affect the viability and BDNF expression of astrocytes. Both co-culturing of neurons with astrocytes and addition of BDNF ameliorated GdCl3-induced neurotoxicity by decreasing ROS generation and facilitating recovery of BDNF levels. The results obtained suggest that astrocytes in the CNS may protect neurons from GdCl3-induced impairment through secreting BDNF and thus up-regulating BDNF expression and interfering with Gd3+-induced cell signaling in neurons. A possible molecular mechanism is suggested which should be helpful in understand- ing the neurotoxic actions of gadolinium probes .展开更多
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.
基金funded by the National Natural Science Foundation of China (20901005 and 20637010)the Research Fund for the Doctoral Program of Higher Education (200800011056)
文摘Gadolinium (Gd3+) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd3+ on neurons in the complex central nervous system (CNS), the neurotoxic actions of GdCl3 have been investigated in both neuron monoculture and astrocyte-neuron co-culture systems. Measurements of lactate dehydrogenase release showed that GdCl3 causes significant cell death of monocultured neurons as a result of reactive oxygen species (ROS) generation and down-regulation of brain-derived neurotrophic factor (BDNF). However, GdCl3 does not affect the viability and BDNF expression of astrocytes. Both co-culturing of neurons with astrocytes and addition of BDNF ameliorated GdCl3-induced neurotoxicity by decreasing ROS generation and facilitating recovery of BDNF levels. The results obtained suggest that astrocytes in the CNS may protect neurons from GdCl3-induced impairment through secreting BDNF and thus up-regulating BDNF expression and interfering with Gd3+-induced cell signaling in neurons. A possible molecular mechanism is suggested which should be helpful in understand- ing the neurotoxic actions of gadolinium probes .
