Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
Stress. 2010 Mar;13(2):95-105. doi: 10.3109/10253890902951786.
Several clinical and preclinical studies have indicated that hippocampal shrinkage and decreased neurogenesis are implicated in the pathology of depression. Recent animal studies have shown, however, that the development of depression-related symptoms may take place through neurogenesis-independent pathways. To evaluate whether the stress-induced morphological changes in the hippocampal formation are causally related to the development of anhedonia-like symptoms, we combined the chronic mild stress (CMS) rat model of depression with stereological estimations of the number of proliferating progenitors, the total number of granule cells, and the volume of the ventral hippocampal formation (VHF). First, we found that stress-susceptible and stress-resilient animals, as categorized according to the behavioral read-out, both have a decrease in hippocampal cell proliferation. Our results also indicated that the anhedonia-like state in CMS rats develops prior to maximal suppression of cell proliferation, but correlates with a reduction in the total number of granule cells in the VHF. Furthermore, recovery from depression-related symptoms correlated with re-establishment of proliferation rates, but not with the total number of granule cells. Notably, decreases in the number of granule cells occurred independently of the induction of an anhedonia-like phenotype. There were no stress-induced changes in the volume of the VHF. We conclude that cell proliferation and a reduction in the total number of granule cells in the VHF are triggered by chronic stress, but do not associate with development of an anhedonia-like state in rats.
几项临床和临床前研究表明，海马体萎缩和神经发生减少与抑郁症的病理学有关。然而，最近的动物研究表明，抑郁相关症状的发展可能通过与神经发生无关的途径发生。为了评估海马结构中的应激诱导的形态变化是否与快感缺失样症状的发展有因果关系，我们将慢性轻度应激 (CMS) 大鼠抑郁症模型与增殖祖细胞数量、颗粒细胞总数和腹侧海马体积 (VHF) 的体视学估计相结合。首先，我们发现根据行为读数进行分类的应激易感和应激耐受动物都存在海马细胞增殖减少。我们的结果还表明，CMS 大鼠的快感缺失样状态在细胞增殖受到最大抑制之前发展，但与 VHF 中颗粒细胞总数减少相关。此外，与抑郁相关症状的恢复相关的是增殖率的重新建立，而不是颗粒细胞的总数。值得注意的是，颗粒细胞数量的减少与快感缺失样表型的诱导无关。VHF 的体积没有应激诱导的变化。我们得出结论，细胞增殖和 VHF 中颗粒细胞总数的减少是由慢性应激引起的，但与大鼠快感缺失样状态的发展无关。
