Long-term environmental enrichment affects microglial morphology in middle age mice
Long-term environmental enrichment affects microglial morphology in middle age mice
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DOI：
10.18632/aging.101923
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发表时间：
2019-04-30
期刊：
影响因子：
5.2
通讯作者：
Cao, Lei
中科院分区：
文献类型：
--
作者：
Ali, Seemaab;Liu, Xianglan;Cao, Lei
衰老与中枢神经系统炎症增加有关，这在很大程度上是由于小胶质细胞功能失调。环境富集（EE）为研究生活方式因素在年龄相关性神经炎症和小胶质细胞功能障碍发展中的动力学提供了一个模型。EE在各种动物模型中导致学习和记忆，新陈代谢和心理健康的改善。我们最近报道说，在中年实施EE促进健康老龄化。在本研究中，我们研究了EE是否影响小胶质细胞形态，以及EE是否与小胶质细胞和神经炎症标志物表达的变化相关。炎症细胞因子和MHC-II在10个月大的小鼠中12个月EE后减少。长期EE为7.5个月导致广泛的增加在海马，下丘脑，杏仁核的免疫组织化学检测到的Iba 1表达。小胶质细胞形态学的定量显示这三个脑区域中的肥大和分支，而没有小胶质细胞密度的增加。这些数据表明，在中年实施的长期EE导致与标准实验室住房中的正常老化不同的小胶质细胞状态，在特定的大脑区域，与神经炎症标志物减少和全身代谢改善相关。
Aging is associated with increased central nervous system inflammation, in large part due to dysfunctional microglia. Environmental enrichment (EE) provides a model for studying the dynamics of lifestyle factors in the development of age-related neuroinflammation and microglial dysfunction. EE results in improvements in learning and memory, metabolism, and mental health in a variety of animal models. We recently reported that implementing EE in middle age promotes healthy aging. In the present study, we investigated whether EE influences microglial morphology, and whether EE is associated with changes in expression of microglial and neuroinflammatory markers. Inflammatory cytokines and MHC-II were reduced following 12-month EE in 10-month-old mice. Long-term EE for 7.5 months resulted in broad increases in Iba1 expression in hippocampus, hypothalamus, and amygdala detected by immunohistochemistry. Quantification of microglial morphology reveal both hypertrophy and ramification in these three brain regions, without increases in microglial cell density. These data indicate that long-term EE implemented in middle age results in a microglial state distinct from that of normal aging in standard laboratory housing, in specific brain regions, associated with reduced neuroinflammatory markers and improvement of systemic metabolism.