Early enriched physical environment reverses impairments of the hippocampus, but not medial prefrontal cortex, of socially-isolated mice
Early enriched physical environment reverses impairments of the hippocampus, but not medial prefrontal cortex, of socially-isolated mice
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DOI：
10.1016/j.bbi.2017.04.009
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发表时间：
2017-08-01
影响因子：
15.1
通讯作者：
Xiao, Ming
中科院分区：
文献类型：
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作者：
Cao, Min;Pu, Tinglin;Xiao, Ming
早期社会隔离（SI）会产生各种情绪，行为和认知异常。相反，丰富的环境（EE），一个复杂的社会和物理结构，对大脑的可塑性和发展提供了有益的影响。然而，是否排他性的物理EE是足以扭转早期SI的不良后果仍不清楚。在这里，我们报告说，1个月大的孤独小鼠在EE中生活8周，纠正了空间认知功能障碍，但没有改善社会互动缺陷和增加焦虑样行为。病理分析显示，丰富的环境减少了海马中的细胞凋亡、突触蛋白丢失、髓鞘形成缺陷和小胶质细胞活化，但对单独饲养的小鼠的内侧前额叶皮质（mPFC）却没有减少。此外，增加核因子-κ B和白细胞介素-1 β水平，下调脑源性神经营养因子信号通路正常化，而不是这些动物的mPFC海马。我们的研究结果显示，在治疗青春期SI小鼠的脑损伤中，物理EE具有脑区域特异性的有效性，完全逆转了依赖于大脑皮层的认知功能障碍，但没有减轻mPFC相关的焦虑和社会互动缺陷。这一发现强调了社会生活对早期大脑发育的不可替代的作用。(C)2017爱思唯尔公司All rights reserved.
Early social isolation (SI) produces a variety of emotional, behavioral and cognitive abnormalities. Conversely, environmental enrichment (EE), a complicated social and physical construct, offers beneficial effects on brain plasticity and development. However, whether or not exclusive physical EE is sufficient to reverse the adverse consequences of early SI remains unclear. Here we reported that 1 month-old solitary mice housed in the EE for 8 weeks corrected spatial cognitive dysfunction, but did not ameliorate social interaction deficits and increased anxiety-like behavior. Pathological analyses revealed that the enriched environment decreased cellular apoptosis, synaptic protein loss, myelination defect and microglial activation in the hippocampus, but not medial prefrontal cortex (mPFC) of mice housed singly. Moreover, increased nuclear factor-kappaB and interleukin-1 beta levels, and downregulation of brain-derived neurotrophic factor signaling pathway were normalized in the hippocampus rather than mPFC of these animals. Our results revealed a brain region-specific effectiveness of physical EE in remediating brain impairment of adolescent SI mice, with a complete reversal of hippocampus-dependent cognitive dysfunctions, but without mitigation of mPFC associated anxiety and social interaction defects. This finding emphasizes the irreplaceable role of social life for the early brain development. (C) 2017 Elsevier Inc. All rights reserved.