New insights into BDNF function in depression and anxiety
New insights into BDNF function in depression and anxiety
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DOI：
10.1038/nn1971
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发表时间：
2007-09-01
影响因子：
25
通讯作者：
Lu, Bai
中科院分区：
文献类型：
--
作者：
Martinowich, Keri;Manji, Husseini;Lu, Bai
“抑郁症的神经营养因子假说”主要基于压力或抗抑郁治疗与脑源性神经营养因子（BDNF）下调或上调之间的相关性。涉及 BDNF 及其受体酪氨酸激酶 TrkB 的信号通路的基因破坏似乎不会导致抑郁行为，但确实会妨碍抗抑郁药物的作用。因此，BDNF 可能是抗抑郁药的靶点，但不是抑郁或焦虑的唯一调节因素。 BDNF 细胞生物学的进展，包括其通过多个启动子的转录、运输和分泌，可能为其在情绪障碍中的作用提供新的见解。此外，由于前体 proBDNF 和成熟蛋白 mBDNF 会对细胞功能产生相反的影响，因此应考虑 proBDNF 及其裂解对情绪的影响。 mBDNF 和 proBDNF 对长期增强和长期抑制的相反影响可能导致 BDNF 对大脑压力和奖励系统介导的行为的二分法。
The 'neurotrophin hypothesis of depression' is based largely on correlations between stress or antidepressant treatment and down- or upregulation, respectively, of brain-derived neurotrophic factor ( BDNF). Genetic disruption of the signaling pathways involving BDNF and its receptor, the tyrosine kinase TrkB, does not seem to cause depressive behaviors, but does hamper the effect of antidepressant drugs. Thus, BDNF may be a target of antidepressants, but not the sole mediator of depression or anxiety. Advances in BDNF cell biology, including its transcription through multiple promoters, trafficking and secretion, may provide new insights into its role in mood disorders. Moreover, as the precursor proBDNF and the mature protein mBDNF can elicit opposite effects on cellular functions, the impact of proBDNF and its cleavage on mood should be considered. Opposing influences of mBDNF and proBDNF on long-term potentiation and long-term depression might contribute to the dichotomy of BDNF actions on behaviors mediated by the brain stress and reward systems.