The neuron-astrocyte-microglia triad involvement in neuroinflammaging mechanisms in the CA3 hippocampus of memory-impaired aged rats
The neuron-astrocyte-microglia triad involvement in neuroinflammaging mechanisms in the CA3 hippocampus of memory-impaired aged rats
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DOI：
10.1016/j.exger.2016.07.011
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发表时间：
2016-10-01
影响因子：
3.9
通讯作者：
Giovannini, Maria Grazia
中科院分区：
文献类型：
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作者：
Lana, Daniele;Iovino, Ludovica;Giovannini, Maria Grazia
本研究观察了炎症对青年大鼠海马CA 3区锥体层（SP）、透明层（SL）和放射层（SR）神经元-星形胶质细胞-小胶质细胞三联体的记忆编码、促炎蛋白质的定性和定量改变、细胞凋亡、神经元变性和形态学改变的影响（3个月）和老年大鼠老年大鼠在抑制性回避任务中表现出短时记忆障碍，SP中iNOS表达增加和p38 MAPK激活，SP区凋亡神经元增多，SL区异位神经元增多，CA 3区锥体神经元减少。老年大鼠海马CA 3区星形胶质细胞数量减少，分支长度减少，形态学表现为树枝状突起。总的和激活的小胶质细胞增加的三个CA 3亚区的老年大鼠。在老年大鼠CA 3，星形胶质细胞包围异位变性神经元，在其周围形成“微疤痕”。星形胶质细胞分支浸润神经元胞体，并与活化的小胶质细胞一起形成“三联体”。老年大鼠海马CA 3区SL和SR的星形胶质细胞和小胶质细胞数量明显增多，它们在异位神经元的破碎和吞噬中起协同作用，炎症诱导的老年大鼠海马CA 3区星形胶质细胞和小胶质细胞的改变可能有助于清除轻度炎症和凋亡产生的神经元碎片。这些事件可能是许多神经退行性过程的共同机制。它们出现的频率可能取决于神经退行性变的负担和严重程度，或者可能是神经退行性变的原因。靶向三联体可以代表一种治疗策略，其可以控制炎症过程和进一步细胞损伤向邻近细胞的扩散。(C)2016 Elsevier Inc. All rights reserved.
We examined the effects of inflammaging on memory encoding, and qualitative and quantitative modifications on proinflammatory proteins, apoptosis, neurodegeneration and morphological changes of neuron-astrocyte-microglia triads in CA3 Stratum Pyramidale (SP), Stratum Lucidum (SL) and Stratum Radiatum (SR) of young (3 months) and aged rats (20 months).Aged rats showed short-term memory impairments in the inhibitory avoidance task, increased expression of iNOS and activation of p38MAPK in SP, increase of apoptotic neurons in SP and of ectopic neurons in SL, and decrease of CA3 pyramidal neurons. The number of astrocytes and their branches length decreased in the three CA3 subregions of aged rats, with morphological signs of clasmatodendrosis. Total and activated microglia increased in the three CA3 subregions of aged rats. In aged rats CA3, astrocytes surrounded ectopic degenerating neurons forming "micro scars" around them. Astrocyte branches infiltrated the neuronal cell body, and, together with activated microglia formed "triads". In the triads, significantly more numerous in CA3 SL and SR of aged rats, astrocytes and microglia cooperated in fragmentation and phagocytosis of ectopic neurons.Inflammaging-induced modifications of astrocytes and microglia in CA3 of aged rats may help clearing neuronal debris derived from low-grade inflammation and apoptosis. These events might be common mechanisms underlying many neurodegenerative processes. The frequency to which they appear might depend upon, or might be the cause of, the burden and severity of neurodegeneration. Targeting the triads may represent a therapeutic strategy which may control inflammatory processes and spread of further cellular damage to neighboring cells. (C) 2016 Elsevier Inc. All rights reserved.