AIM2 deletion promotes neuroplasticity and spatial memory of mice
AIM2 deletion promotes neuroplasticity and spatial memory of mice
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AIM2缺失促进小鼠神经可塑性和空间记忆
DOI：
10.1016/j.brainresbull.2019.07.011
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发表时间：
2019-10-01
影响因子：
3.8
通讯作者：
Zhang, Meijuan
中科院分区：
文献类型：
--
作者：
Chen, Jian;Shu, Shu;Zhang, Meijuan
黑色素瘤2 （AIM2）中缺失的基因感知损伤相关分子模式（DAMPs）并招募凋亡斑点样蛋白（ASC）和caspase-1，形成脑炎症和神经元焦亡的分子平台。本研究发现AIM2在6月龄APP/PS1小鼠海马中表达上调，并进一步探讨AIM2在空间记忆、长时程增强（LTP）和突触形态中的作用。通过Morris水迷宫和y迷宫实验，我们发现AIM2缺失对小鼠的空间记忆有显著的促进作用。此外，AIM2在海马CA1神经元中广泛表达。AIM2的缺失促进了海马切片的LTP，改变了树突结构，特别是增加了树突棘密度。利用转录芯片技术，我们发现AIM2-/-小鼠与ANT小鼠相比，有41个基因下调，16个基因上调（fold change > = 2.0, p < 0.05）。我们进一步通过Western blotting和qPCR验证了AIM2敲除显著改变了海马Pten、Homer1和Ppp2r3a水平。此外，AIM2缺失后AKT磷酸化显著增强。综上所述，我们的数据表明，AIM2缺失促进了空间记忆、突触可塑性和树突分支，这可能与其对Pten和Ppp2r3a的抑制作用以及对Homer 1和AKT通路的刺激作用有关。
Absent in melanoma 2 (AIM2) senses damaged-associated molecular patterns (DAMPs) and recruits apoptosis speck-like protein (ASC) and caspase-1 to form a molecular platform for cerebral inflammation and neuronal pyroptosis. Here, we found that AIM2 was up-regulated in the hippocampus of 6-months-old APP/PS1 mice and further investigated the role of AIM2 in spatial memory, long term potentiation (LTP) and synaptic morphology. Our study demonstrated that AIM2 deletion remarkably promoted spatial memory of mice using Morris Water Maze test and Y-Maze test. In addition, AIM2 was found to be widely expressed in the CA1 neurons in the hippocampus. AIM2 deletion facilitated LTP in hippocampal slices and altered the structure of dendrites, especially increased the dendritic spine densities. Using transcriptional microarray, we found that 41 genes were down-regulated and 16 genes were up-regulated in AIM2-/- mice (fold change > = 2.0 and p < 0.05) compared to ANT mice. We further verificated that AIM2 knockout significantly altered hippocampal Pten, Homer1 and Ppp2r3a levels with Western blotting and qPCR. Additionally, phosphorylation of AKT was profoundly enhanced after AIM2 deletion. Collectivelly, our data indicated that AIM2 deletion promoted spatial memory, synaptic plasticity and dendrite branching, which was probably related to its repressive effects on Pten and Ppp2r3a and stimulative effects on Homer 1 and AKT pathways.