Neuroinflammation in Animal Models of Fatigue
Neuroinflammation in Animal Models of Fatigue
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DOI：
10.3233/nib-130073
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Cui, Yilong
中科院分区：
文献类型：
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作者：
Kataoka, Yosky;Yamato, Masanori;Cui, Yilong
我们已经开发了各种神经炎症和疲劳的动物模型。在这里，介绍了两种类型的模型，使用大鼠：一个是中枢疲劳的模型，通过过度的去极化刺激中枢神经系统（CNS）获得;另一个是免疫疲劳的模型，通过腹腔注射的聚核糖肌苷酸：聚核糖胞苷酸（poly I：C），双链RNA，这模拟病毒感染。在中枢疲劳模型中，我们引入了皮层扩散性抑制（SD），即神经元膜去极化在整个大脑皮层的传播。SD后皮质神经元表达考克斯-2，产生前列腺素（PG），包括PGD（2）。在这种模型中，非快速眼动（非REM）睡眠的量，但不是REM睡眠的量，随后增加了几个小时。非快速眼动睡眠的增加被考克斯-2抑制剂NS-398完全减弱，表明非快速眼动睡眠是由大脑中的野牡丹素的产生诱导的。该系统被认为通过诱导静息行为和非快速眼动睡眠来缓解过度的大脑活动。在免疫疲劳模型中，腹腔注射poly I：C（一种合成的双链RNA）诱导大鼠一过性发热和自发活动抑制。我们已经证明，白细胞介素（IL）-1 β的表达上调，在不同的大脑区域，和脑室注射IL-1受体拮抗剂显着减弱聚I：C诱导的疲劳样行为。米诺环素是中枢神经系统中一种有效的神经炎症抑制剂，用米诺环素预处理可使poly I：C注射对自发活动的抑制作用无效。脑内IL-1 β和内源性拮抗剂的平衡可能调节神经炎症和疲劳样行为。
We have developed various animal models of neuroinflammation and fatigue. Here, two types of models using rats are introduced: one is a model of central fatigue obtained by excessive depolarizing stimuli to the central nervous system (CNS); another is that of immunological fatigue obtained by intraperitoneal injection of polyriboinosinic: polyribocytidylic acid (poly I:C), double-stranded RNA, which mimics viral infection. In the central fatigue model, we introduced cortical spreading depression (SD), the propagation of neuronal membrane depolarization throughout the cerebral cortex. Prostaglandins (PG) including PGD(2) were produced by COX-2 expression in neurons in the cortex following SD. In such a model, the amount of non-rapid eye movement (non-REM) sleep, but not of REM sleep, subsequently increased for several hours. The increase in non-REM sleep was completely attenuated by application of NS-398, a COX-2 inhibitor, indicating that non-REM sleep was induced by the production of prostaglandins in the brain. This system is thought to relieve excessive brain activity by inducing resting behavior and non-REM sleep. In the immunological fatigue model, intraperitoneal administration of poly I:C, a synthetic double-stranded RNA, induced transient fever and suppression of locomotor activity in rats. We have demonstrated that interleukin (IL)-1 beta expression was up-regulated in various brain regions, and that intracerebroventricular infusion of IL-1 receptor antagonist significantly attenuated the poly I:C-induced fatigue-like behavior. Pretreatment with minocycline, a potent suppressor of neuroinflammation in CNS, nullified the suppressive effect on locomotor activity by poly I:C injection. The balance of IL-1 beta and the endogenous antagonist in the brain possibly regulate neuroinflammation and fatigue-like behavior.