Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice.

Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice.
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DOI:
10.1038/srep08932
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发表时间:
2015-03-10
期刊:
影响因子:
4.6
通讯作者:
Furuichi T
Furuichi T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mishima Y;Shinoda Y;Sadakata T;Kojima M;Wakana S;Furuichi T

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慢性压力与焦虑和抑郁症有关,并可能导致体重增加。 Ca2+ 依赖性分泌激活蛋白 2 (CAPS2) 参与胰岛素释放。 Caps2 敲除 (KO) 小鼠表现出体重减轻、葡萄糖诱导的胰岛素释放减少以及异常精神行为。我们通过饮用水长期施用应激激素皮质酮 (CORT) 10 周,该激素会诱发焦虑/抑郁样行为,通常会增加血浆胰岛素水平,并检查 KO 小鼠的应激反应。慢性 CORT 暴露可抑制野生型 (WT) 小鼠应激引起的血清 CORT 升高,但对 KO 小鼠则不然。在 WT 小鼠中,经过 CORT 处理的动物体重增加缓慢,直到第 6 周,但在 KO 小鼠中,体重增加在整个实验期间持续存在,尽管药物与基因型相互作用没有差异。在实验期间,与未处理的动物相比,在 CORT 处理的 KO 小鼠中,食物消耗量没有变化,而水消耗量更高。此外,CORT 处理的 WT 小鼠血清胰岛素和瘦素水平升高,但 KO 小鼠则没有。最后,WT 和 KO 小鼠在给予 CORT 后均表现出焦虑/抑郁样行为。这些结果表明 Caps2 KO 小鼠改变了对 CORT 给药的内分泌反应,同时维持了 CORT 诱导的焦虑/抑郁样行为。
Chronic stress is associated with anxiety and depressive disorders, and can cause weight gain. Ca2+-dependent activator protein for secretion 2 (CAPS2) is involved in insulin release. Caps2 knockout (KO) mice exhibit decreased body weight, reduced glucose-induced insulin release, and abnormal psychiatric behaviors. We chronically administered the stress hormone corticosterone (CORT), which induces anxiety/depressive-like behavior and normally increases plasma insulin levels, via the drinking water for 10 weeks, and we examined the stress response in KO mice. Chronic CORT exposure inhibited stress-induced serum CORT elevation in wild-type (WT) mice, but not in KO mice. Poor weight gain in CORT-treated animals was observed until week 6 in WT mice, but persisted for the entire duration of the experiment in KO mice, although there is no difference in drug*genotype interaction. Among KO mice, food consumption was unchanged, while water consumption was higher, over the duration of the experiment in CORT-treated animals, compared with untreated animals. Moreover, serum insulin and leptin levels were increased in CORT-treated WT mice, but not in KO mice. Lastly, both WT and KO mice displayed anxiety/depressive-like behavior after CORT administration. These results suggest that Caps2 KO mice have altered endocrine responses to CORT administration, while maintaining CORT-induced anxiety/depressive-like behavior.
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