Bjørnebekk Astrid, Mathé Aleksander A, Gruber Susanne H M, Brené Stefan
Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Hippocampus. 2007;17(12):1193-200. doi: 10.1002/hipo.20352.
Genetic background influences the responsiveness to stress and plays a crucial role in the pathophysiology of depression. In an animal model of depression, Flinders Sensitive Line rats, and Sprague Dawley controls we analyzed if 7 weeks of social isolation of adult animals affect the number of newly proliferated cells in the dentate gyrus or mRNAs of Neuropeptide Y (NPY), the NPY-Y1 receptor, nociceptin, BDNF, and the serotonin 5HT1A and 5HT2A receptors, which are molecules involved in hippocampal plasticity. Since depressive illness more frequently affects women than men, and females seem to respond differently to stressful experiences than males, female rats were used in this study. Bromodeoxyuridine, which is a thymidin analogue that is incorporated into the DNA of newly formed cells, was administered during 9 days to even out the effects of hormonal fluctuations. Social isolation increased the number of newly proliferated Bromodeoxyuridine-immunoreactive cells in the Flinders Sensitive Line rats, whereas it had no impact on the number of cells in the Sprague Dawley strain. Group housed Sprague Dawley rats had a higher expression of BDNF, NPY, and the serotonin 5HT2A receptor mRNA than "depressed" Flinders Sensitive Line. Social isolation downregulated these molecules in Sprague Dawley but not in Flinders Sensitive Line rats thereby eliminating the differences between the two strains. We demonstrate strain and gender specific responses to stress induced regulation of factors important for hippocampal plasticity.
遗传背景会影响对应激的反应,并在抑郁症的病理生理学中起关键作用。在抑郁症动物模型——弗林德斯敏感系大鼠和斯普拉格·道利对照大鼠中,我们分析了成年动物7周的社会隔离是否会影响齿状回中新增殖细胞的数量,或者神经肽Y(NPY)、NPY-Y1受体、孤啡肽、脑源性神经营养因子(BDNF)以及5-羟色胺5HT1A和5HT2A受体的mRNA水平,这些都是与海马可塑性相关的分子。由于抑郁症在女性中比在男性中更常见,而且女性似乎对应激经历的反应与男性不同,所以本研究使用了雌性大鼠。溴脱氧尿苷是一种胸腺嘧啶类似物,可掺入新形成细胞的DNA中,在9天内给予溴脱氧尿苷以消除激素波动的影响。社会隔离增加了弗林德斯敏感系大鼠中新增殖的溴脱氧尿苷免疫反应性细胞的数量,而对斯普拉格·道利品系的细胞数量没有影响。群居的斯普拉格·道利大鼠的BDNF、NPY和5-羟色胺5HT2A受体mRNA的表达高于“抑郁”的弗林德斯敏感系大鼠。社会隔离下调了斯普拉格·道利大鼠中这些分子的表达,但对弗林德斯敏感系大鼠没有影响,从而消除了两个品系之间的差异。我们证明了品系和性别对应激诱导的对海马可塑性重要的因子调节的特异性反应。