Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Brain Behav Immun. 2010 Nov;24(8):1340-6. doi: 10.1016/j.bbi.2010.06.012. Epub 2010 Jul 1.
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.
细胞因子白细胞介素 (IL)-15 与经典神经递质 GABA 之间的相互作用已在 IL15Rα 受体敲除小鼠中通过观察记忆缺陷和 GABA 减少得到证实。为了检验 IL15 影响焦虑样行为的假设，没有 IL15、IL15Rα 或共受体 IL2Rγ 的 IL15Rα 敲除小鼠接受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 敲除小鼠的变化大于 IL15 或 IL2Rγ 敲除小鼠。这一意外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。减少的焦虑与相关血清细胞因子的变化无关。然而，Western blot、qPCR 和免疫组织化学均显示 IL15Rα 敲除小鼠的海马体中有轻微的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降低焦虑中起作用，IL15Rα 敲除小鼠用米诺环素治疗，但这并没有导致旷场表现的变化。为了确定 IL15 是否在焦虑中起直接作用，用腹腔注射的方式向野生型小鼠给予 IL15。在测试的实验条件下，这也未能导致旷场行为的变化。因此，IL15Rα 对于正常的焦虑样行为是必不可少的，但在无畏的 IL15Rα 敲除小鼠中抑制神经胶质增生或用 IL15 治疗正常小鼠不会急性调节行为表现。
