Essential role of interleukin-15 receptor in normal anxiety behavior.

Essential role of interleukin-15 receptor in normal anxiety behavior.
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DOI:
10.1016/j.bbi.2010.06.012
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发表时间:
2010-11
影响因子:
15.1
通讯作者:
Pan, Weihong
Pan, Weihong
中科院分区:
医学1区
文献类型:
--
作者:
Wu, Xiaojun;He, Yi;Hsuchou, Hung;Kastin, Abba J.;Rood, Jennifer C.;Pan, Weihong

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通过观察记忆缺陷和 GABA 减少,在 IL15Rα 受体敲除小鼠中显示了细胞因子白细胞介素 (IL)-15 和经典神经递质 GABA 之间的相互作用。为了检验 IL15 影响焦虑样行为的假设,对没有 IL15、IL15Rα 或辅助受体 IL2Rγ 的基因敲除小鼠进行了旷场和高架十字迷宫测试。所有三种品系均表现出焦虑减轻,IL15Rα 敲除小鼠的变化比 IL15 或 IL2Rγ 敲除小鼠的变化更大。这一意想不到的观察结果与报道的缺乏其他促炎细胞因子或其受体的小鼠焦虑增加相反。焦虑的减轻与相关血清细胞因子的变化无关。然而,蛋白质印迹、qPCR和免疫组化均显示IL15Rα敲除小鼠的海马存在轻度小胶质细胞增生和星形胶质细胞增生。为了确定这种神经胶质增生是否在减少焦虑方面发挥作用,IL15Rα 敲除小鼠接受了米诺环素治疗,但这并没有引起旷场表现的变化。为了确定 IL15 是否在焦虑中发挥直接作用,通过腹腔注射 IL15 治疗野生型小鼠。在测试的实验条件下,这也未能引起开放场行为的变化。因此,IL15Rα 对于正常的焦虑样行为至关重要,但在无畏的 IL15Rα 敲除小鼠中抑制神经胶质增生或对正常小鼠进行 IL15 治疗并不能显着调节所测试的行为表现。
The interactions between the cytokine interleukin (IL)-15 and the classical neurotransmitter GABA have been shown in IL15Rα receptor knockout mice by observations of memory deficits and reduction of GABA. To test the hypothesis that IL15 affects anxiety-like behavior, knockout mice without IL15, IL15Rα, or the co-receptor IL2Rγ were subjected to open-field and elevated plus maze tests. All three strains showed reduction of anxiety, with greater changes in the IL15Rα knockout mice than in the IL15 or IL2Rγ knockout mice. This unexpected observation is opposite to the reported increase of anxiety in mice lacking other proinflammatory cytokines or their receptors. The reduced anxiety was not associated with changes in associated serum cytokines. However, western blotting, qPCR, and immunohistochemistry all showed that IL15Rα knockout mice had mild microgliosis and astrogliosis in the hippocampus. To determine whether this gliosis plays a role in decreasing anxiety, IL15Rα knockout mice were treated with minocycline, but this did not cause a change in open field performance. To determine whether IL15 plays a direct role in anxiety, wildtype mice were treated with IL15 by intraperitoneal injection. This also failed to cause a change in open field behavior under the experimental conditions tested. Thus, IL15Rα is essential for normal anxiety-like behavior, but inhibition of gliosis in the fearless IL15Rα knockout mice or IL15 treatment of normal mice did not acutely modulate behavioral performance as tested.
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