Castrén Eero, Võikar Vootele, Rantamäki Tomi
Sigrid Jusélius Laboratory of Molecular Neuroscience, Neuroscience Center, University of Helsinki, PO Box 56, 00014 Helsinki, Finland.
Curr Opin Pharmacol. 2007 Feb;7(1):18-21. doi: 10.1016/j.coph.2006.08.009. Epub 2006 Oct 17.
Major depression is associated with reduced volumes in the hippocampus and prefrontal cortex, whereas antidepressant treatments promote several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation, in the hippocampus. Several neurotrophic factors are associated with depression or antidepressant action. Stress suppresses brain-derived neurotrophic factor (BDNF) synthesis in the hippocampus, at least partially through a sustained modification of chromatin structure. Essentially all antidepressant treatments increase BDNF synthesis and signaling in the hippocampus and prefrontal cortex. This signaling is required for the behavioral effects of antidepressant drugs in rodents, and increased BDNF levels in the hippocampus mimic the behavioral effects of antidepressants. However, injection of BDNF into the mesolimbic dopamine pathway produces an opposing depression-like response. One hypothesis emerging from these data proposes that mood disorders reflect failed function of critical neuronal networks, whereas a gradual network recovery through activity-dependent neuronal plasticity induces the antidepressant effect. Neurotrophic factors themselves do not control mood, but they act as necessary tools in the activity-dependent modulation of networks, the physiological function of which determines how a plastic change influences mood.
重度抑郁症与海马体和前额叶皮质体积减小有关，而抗抑郁治疗可促进海马体中多种形式的神经元可塑性，包括神经发生、突触形成和神经元成熟。几种神经营养因子与抑郁症或抗抑郁作用相关。应激至少部分通过持续改变染色质结构来抑制海马体中脑源性神经营养因子（BDNF）的合成。基本上所有的抗抑郁治疗都会增加海马体和前额叶皮质中BDNF的合成和信号传导。这种信号传导是抗抑郁药物在啮齿动物中产生行为效应所必需的，海马体中BDNF水平的升高模拟了抗抑郁药物的行为效应。然而，将BDNF注射到中脑边缘多巴胺通路会产生相反的抑郁样反应。从这些数据中得出的一个假设是，情绪障碍反映了关键神经网络的功能失调，而通过依赖活动的神经元可塑性实现的逐渐网络恢复会诱导抗抑郁作用。神经营养因子本身并不控制情绪，但它们在依赖活动的网络调节中充当必要工具，网络的生理功能决定了可塑性变化如何影响情绪。
