IL-13-Mediated Regulation of Learning and Memory
IL-13-Mediated Regulation of Learning and Memory
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DOI：
10.4049/jimmunol.1601546
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发表时间：
2017-04-01
影响因子：
4.4
通讯作者：
Brombacher, Frank
中科院分区：
文献类型：
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作者：
Brombacher, Tiroyaone M.;Nono, Justin K.;Brombacher, Frank
促炎细胞因子在认知功能中的作用已被研究，根据细胞因子的不同，其可能产生有益的影响，也可能产生有害的影响。最近，2 型 IL-4 已被证明在认知中发挥作用。在这项研究中，我们利用 Morris 水迷宫任务证明，IL-13 缺陷小鼠的工作记忆和参考记忆显着受损，这两种功能对于有效的复杂学习至关重要。在学习过程中，野生型小鼠脑膜中CD4+T细胞的数量增加，IL-13的产生增加，而Morris水迷宫训练的IL-4和IL-13缺陷型小鼠均不能增加脑膜中CD4+T细胞的数量。从机制上讲，我们发现 IL-13 能够刺激初级星形胶质细胞产生脑源性神经营养因子，从而促进认知功能。此外，经过Morris水迷宫训练的野生型小鼠能够增加海马中星形胶质细胞产生的胶质纤维酸性蛋白，而在经过Morris水迷宫训练的IL-4和IL-13缺陷型小鼠中，该蛋白受到损害。总的来说，这项研究强烈表明，Th2 细胞因子（不仅是 IL-4，还有 IL-13）通过刺激脑膜和海马的星形胶质细胞参与认知功能。这些结果对于未来开发与神经系统疾病相关的治疗方法可能很重要，例如帕金森病相关痴呆和艾滋病毒相关痴呆等。
The role of proinflammatory cytokines in cognitive function has been investigated with both beneficial and possible detrimental effects, depending on the cytokine. More recently, the type 2 IL-4 has been demonstrated to play a role in cognition. In this study, using the Morris water maze task, we demonstrate that IL-13-deficient mice are significantly impaired in working memory as well as attenuated reference memory, both functions essential for effective complex learning. During the learning process, wild-type mice increased the number of CD4(+) T cells in the meninges and production of IL-13, whereas neither Morris water maze-trained IL-4 nor trained IL-13-deficient mice were able to increase CD4(+) T cells in the meninges. Mechanistically, we showed that IL-13 is able to stimulate primary astrocytes to produce brain-derived neurotrophic factor, which does foster cognitive functions. Moreover, Morris water maze-trained wild-type mice were able to increase astrocyte-produced glial fibrillary acidic protein in the hippocampus, which was impaired in Morris water maze-trained IL-4-and IL-13-deficient mice. Collectively, this study strongly suggests that the Th2 cytokines, not only IL-4 but also IL-13, are involved in cognitive functions by stimulating astrocytes from the meninges and hippocampus. These results may be important for future development of therapeutic approaches associated with neurologic disorders such as Parkinson disease-associated dementia and HIV-associated dementia among others.