Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice
Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice
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DOI：
10.1016/j.ejphar.2008.01.014
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发表时间：
2008-03-31
影响因子：
5
通讯作者：
Hutson, Peter H.
中科院分区：
文献类型：
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作者：
Murray, Fraser;Smith, David W.;Hutson, Peter H.
下丘脑-垂体-肾上腺轴（HPA）失调与重度抑郁症有关，大多数常用的抑郁症动物模型已被证明可提高血浆皮质酮的循环水平。我们比较了慢性和急性皮质酮给药对CD1小鼠海马细胞增殖（通过BrdU免疫组织化学测量）、海马体积以及焦虑（光暗箱）和抑郁（强迫游泳试验）样行为的影响。我们还研究了长期服用氟西汀和丙咪嗪对这些参数的影响。慢性（14天）而非急性皮质酮治疗导致海马细胞增殖和颗粒细胞层体积减少，丙咪嗪和氟西汀联合使用可防止这些变化。相比之下，皮质酮治疗急性期和第7天，而不是第14天或第21天，在强迫游泳试验中导致“抑郁”表型。用皮质酮治疗14天的小鼠在明暗箱中也出现了焦虑表型，但只有在重复测试后才会出现。本研究的结果表明，长期适度升高的皮质酮足以诱导海马体的细胞变化，而这种变化是由长期服用抗抑郁药所预防的。(C) 2008 Elsevier B.V.版权所有
A dysregulated hypothalamic-pituitary-adrenal axis (HPA) has been implicated in major depressive disorder and most commonly used animal models of depression have been shown to elevate circulating levels of plasma corticosterone. We have compared the effects of chronic and acute corticosterone administration on hippocampal cell proliferation (as measured by BrdU immunohistochemistry), hippocampal volume and the appearance of anxiety (light dark box) and depression (forced swim test) like behaviours in CD1 mice. We have also examined the effects of chronic administration of fluoxetine and imipramine on these parameters. Chronic (14 days) but not acute treatment with corticosterone resulted in reduced hippocampal cell proliferation and granule cell layer volume, these changes were prevented by co-administration of imipramine and fluoxetine. In contrast, acute and 7 day but not 14 or 21 day treatment with corticosterone gave rise to a "depressed" phenotype in the forced swim test. Mice treated for 14 days with corticosterone also developed an anxious phenotype in the light dark box but only upon repeated testing. The results presented here demonstrate that moderately elevated corticosterone for a prolonged period is sufficient to induce cellular changes in the hippocampus that are prevented by chronic administration of antidepressants. (C) 2008 Elsevier B.V. All rights reserved.