Castrén Eero, Kojima Masami
Neuroscience Center, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland.
Biomedical Research Institute, Advanced Industrial Science and Technology (AIST), Osaka 563-8577, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan.
Neurobiol Dis. 2017 Jan;97(Pt B):119-126. doi: 10.1016/j.nbd.2016.07.010. Epub 2016 Jul 15.
Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment. These data, together with a wealth of reports using different animal models with depression-like behavior or manipulation of expression of BDNF or its receptor TrkB have implicated BDNF in the pathophysiology of depression as well as in the mechanism of action of antidepressant treatments. Recent findings have shown that posttranslational processing of BDNF gene product can yield different molecular entities that differently influence signaling through BNDF receptor TrkB and the pan-neurotrophin receptor p75. We will here review these data and discuss new insights into the possible pathophysiological roles of those new BDNF subtypes as well as recent findings on the role of BDNF mediated neuronal plasticity in mood disorders and their treatments.
抑郁症患者大脑和血清中的脑源性神经营养因子(BDNF)水平降低,并且至少血清水平的降低在成功治疗后是可逆的。这些数据,连同大量使用具有抑郁样行为的不同动物模型或对BDNF及其受体TrkB的表达进行操纵的报告,表明BDNF参与了抑郁症的病理生理学以及抗抑郁治疗的作用机制。最近的研究发现,BDNF基因产物的翻译后加工可以产生不同的分子实体,这些分子实体对通过BDNF受体TrkB和泛神经营养因子受体p75的信号传导有不同的影响。我们将在此回顾这些数据,并讨论这些新的BDNF亚型可能的病理生理作用的新见解,以及关于BDNF介导的神经元可塑性在情绪障碍及其治疗中的作用的最新发现。