Department of Psychology & Neuroscience, Duke University, Durham, NC 27708, USA.
Brain Behav Immun. 2012 Mar;26(3):500-10. doi: 10.1016/j.bbi.2012.01.003. Epub 2012 Jan 20.
Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Environmental enrichment (EE) in rodents increases neurogenesis, enhances cognition, and promotes recovery from injury. However, little is known about the effects of EE on glia (astrocytes and microglia). Given their importance in neural repair, we predicted that EE would modulate glial phenotype and/or function within the hippocampus. Adult male rats were housed either 12 h/day in an enriched environment or in a standard home cage. Rats were injected with BrdU at 1 week, and after 7 weeks, half of the rats from each housing group were injected with lipopolysaccharide (LPS), and cytokine and chemokine expression was assessed within the periphery, hippocampus and cortex. Enriched rats had a markedly blunted pro-inflammatory response to LPS within the hippocampus. Specifically, expression of the chemokines Ccl2, Ccl3 and Cxcl2, several members of the tumor necrosis factor (TNF) family, and the pro-inflammatory cytokine IL-1β were all significantly decreased following LPS administration in EE rats compared to controls. EE did not impact the inflammatory response to LPS in the cortex. Moreover, EE significantly increased both astrocyte (GFAP+) and microglia (Iba1+) antigen expression within the DG, but not in the CA1, CA3, or cortex. Measures of neurogenesis were not impacted by EE (BrdU and DCX staining), although hippocampal BDNF mRNA was significantly increased by EE. This study demonstrates the importance of environmental factors on the function of the immune system specifically within the brain, which can have profound effects on neural function.
神经发生是成年海马齿状回（DG）中的一个特征明显的现象。环境丰富（EE）在啮齿动物中增加神经发生，增强认知，并促进损伤后的恢复。然而，关于 EE 对神经胶质（星形胶质细胞和小胶质细胞）的影响知之甚少。鉴于它们在神经修复中的重要性，我们预测 EE 会调节海马内的神经胶质表型和/或功能。成年雄性大鼠每天 12 小时分别饲养在丰富环境或标准笼中。大鼠在 1 周时注射 BrdU，7 周后，每组一半的大鼠接受脂多糖（LPS）注射，并评估外周血、海马和皮质中的细胞因子和趋化因子表达。丰富环境中的大鼠在海马内对 LPS 的促炎反应明显减弱。具体而言，与对照组相比，LPS 给药后，趋化因子 Ccl2、Ccl3 和 Cxcl2、几种肿瘤坏死因子（TNF）家族成员以及促炎细胞因子 IL-1β 的表达在 EE 大鼠中均显著降低。EE 对 LPS 在皮质中的炎症反应没有影响。此外，EE 显著增加 DG 中的星形胶质细胞（GFAP+）和小胶质细胞（Iba1+）抗原表达，但在 CA1、CA3 或皮质中没有影响。EE 没有影响神经发生的测量（BrdU 和 DCX 染色），尽管 EE 显著增加了海马 BDNF mRNA。这项研究表明环境因素对大脑中免疫系统功能的重要性，这可能对神经功能产生深远影响。
