Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus.

Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus.
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DOI:
10.1016/j.bbi.2012.01.003
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发表时间:
2012-03
影响因子:
15.1
通讯作者:
Bilbo, Staci D.
Bilbo, Staci D.
中科院分区:
医学1区
文献类型:
--
作者:
Williamson, Lauren L.;Chao, Agnes;Bilbo, Staci D.

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神经发生是成人海马齿状回(DG)内的一种特征明显的现象。环境富集(EE)能促进啮齿动物的神经发生,增强认知能力,促进损伤后的恢复。然而,EE对胶质细胞(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会调节海马内的胶质细胞表型和/或功能。成年雄性大鼠被安置在一个丰富的环境中,或在一个标准的家庭笼子中,每天12小时。第1周给大鼠注射BrdU,第7周后,每组各一半大鼠注射脂多糖(LPS),检测外周、海马和皮质内细胞因子和趋化因子的表达。富脂大鼠对海马体内LPS的促炎反应明显减弱。具体而言,与对照组相比,LPS处理后,EE大鼠的趋化因子Ccl2、Ccl3和Cxcl2、肿瘤坏死因子(TNF)家族的几个成员以及促炎细胞因子IL-1β的表达均显著降低。EE不影响皮层对LPS的炎症反应。此外,EE显著增加了DG内星形胶质细胞(GFAP+)和小胶质细胞(Iba1+)抗原的表达,但在CA1、CA3和皮质中没有。虽然海马BDNF mRNA被EE显著增加,但EE并未影响神经发生的测量(BrdU和DCX染色)。这项研究证明了环境因素对免疫系统功能的重要性,特别是在大脑内,这可能对神经功能产生深远的影响。
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.
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