Effects of environmental enrichment on white matter glial responses in a mouse model of chronic cerebral hypoperfusion.
Effects of environmental enrichment on white matter glial responses in a mouse model of chronic cerebral hypoperfusion.
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DOI：
10.1186/s12974-017-0850-5
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发表时间：
2017-04-11
影响因子：
9.3
通讯作者：
Kalaria RN
中科院分区：
文献类型：
--
作者：
Hase Y;Craggs L;Hase M;Stevenson W;Slade J;Lopez D;Mehta R;Chen A;Liang D;Oakley A;Ihara M;Horsburgh K;Kalaria RN
本研究旨在探讨丰富环境（EE）对双侧颈总动脉狭窄（BCAS）所致小鼠慢性脑低灌注模型白色胶质细胞变化的有益作用。共74只野生型雄性C57 BL/6 J小鼠接受BCAS或假手术。手术后一周，将小鼠随机分配到三个不同的组中，这些组具有不同量的EE标准圈养，无EE条件（std），每天3小时EE的有限暴露（3小时）和12周的全时暴露于EE（完全）。在BCAS手术后16周，在安乐死前评估行为和认知功能。分析脑组织的神经胶质增生程度，包括星形胶质细胞和小胶质细胞的形态学变化。慢性脑灌注不足（或BCAS）增加的clasmatodendrocytes（受损的星形胶质细胞）与水通道蛋白-4免疫反应性的破坏和程度增加的小胶质细胞活化/增殖。BCAS还损害了行为和认知功能。这些变化显着衰减，有限的曝光相比，全职暴露于EE。我们的研究结果表明，中度或有限的暴露于EE大大减少了胶质细胞的损伤/激活。我们的研究结果还表明，适度而不是持续暴露于EE是有益的患者与皮质下缺血性血管性痴呆的特点是白色物质疾病相关的炎症。
This study was designed to explore the beneficial effects of environmental enrichment (EE) on white matter glial changes in a mouse model of chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS). A total of 74 wild-type male C57BL/6J mice underwent BCAS or sham surgery. One week after surgery, the mice were randomly assigned into three different groups having varied amounts of EE—standard housing with no EE conditions (std), limited exposure with 3 h EE a day (3 h) and full-time exposure to EE (full) for 12 weeks. At 16 weeks after BCAS surgery, behavioural and cognitive function were assessed prior to euthanasia. Brain tissues were analysed for the degree of gliosis including morphological changes in astrocytes and microglia. Chronic cerebral hypoperfusion (or BCAS) increased clasmatodendrocytes (damaged astrocytes) with disruption of aquaporin-4 immunoreactivity and an increased degree of microglial activation/proliferation. BCAS also impaired behavioural and cognitive function. These changes were significantly attenuated, by limited exposure compared to full-time exposure to EE. Our results suggest that moderate or limited exposure to EE substantially reduced glial damage/activation. Our findings also suggest moderate rather than continuous exposure to EE is beneficial for patients with subcortical ischaemic vascular dementia characterised by white matter disease-related inflammation.