Keilhoff Gerburg, Becker Axel, Grecksch Gisela, Bernstein Hans-Gert, Wolf Gerald
Institute of Medical Neurobiology, University of Magdeburg, Magdeburg, Germany.
Neuropsychopharmacology. 2006 Jun;31(6):1165-76. doi: 10.1038/sj.npp.1300924.
Growing evidence indicates that alterations of neuroplasticity may contribute to the pathophysiology of depression. In contrast, various antidepressants increase adult hippocampal neurogenesis and block the effects of stress. These findings result in the 'neurogenesis hypothesis of depression'. The present study seeks to determine out whether cell proliferation is altered in the hippocampus, subventricular zone (SVZ), and basolateral amygdala of adult rats exposed to bilateral olfactory bulbectomy, another established model of depression and, if so, how imipramine effects bulbectomy-induced changes of cell genesis. Bulbectomy results in a significant reduction of cell proliferation in the hippocampus and SVZ, an effect that is normalized by subchronic doses of imipramine. Moreover, an increase in cell genesis in the basolateral amygdala, which is not affected by imipramine, is demonstrated. TUNEL staining indicates an enhanced apoptosis after bulbectomy in the SVZ that cannot be reduced by imipramine. Cell death rates in the hippocampus and amygdala are not affected by bulbectomy. The opposing effects of bulbectomy and imipramine treatment in the hippocampus and amygdala demonstrate that these structures of the limbic system, both integrated in emotional processing, react quite differently with regard to neuroplasticity. Further to this, we discuss a possible link between the pathogenesis of depression and changed neuronal plasticity in the SVZ.
越来越多的证据表明，神经可塑性的改变可能导致抑郁症的病理生理过程。相比之下，各种抗抑郁药可增加成年海马体神经发生并阻断应激的影响。这些发现导致了“抑郁症的神经发生假说”。本研究旨在确定双侧嗅球切除的成年大鼠海马体、脑室下区（SVZ）和基底外侧杏仁核中的细胞增殖是否发生改变，嗅球切除是另一种已确立的抑郁症模型，以及如果发生改变，丙咪嗪如何影响嗅球切除诱导的细胞生成变化。嗅球切除导致海马体和SVZ中的细胞增殖显著减少，亚慢性剂量的丙咪嗪可使这种效应恢复正常。此外，还证明了基底外侧杏仁核中的细胞生成增加，且不受丙咪嗪影响。TUNEL染色表明，嗅球切除后SVZ中的细胞凋亡增加，丙咪嗪无法使其减少。嗅球切除对海马体和杏仁核中的细胞死亡率没有影响。嗅球切除和丙咪嗪治疗对海马体和杏仁核产生的相反作用表明，边缘系统的这些结构虽都参与情绪处理，但在神经可塑性方面反应截然不同。除此之外，我们还讨论了抑郁症发病机制与SVZ中神经元可塑性变化之间的可能联系。
