Journal
BRAIN RESEARCH BULLETIN
Volume 152, Issue -, Pages 85-94Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2019.07.011
Keywords
AIM2; Spatial memory; Synaptic plasticity; LTP; Microarray
Categories
Funding
- National Natural Science Foundation of China [81571135, 81630028]
- Nanjing Outstanding Youth Foundation [JQX15003, JQX16024]
- Jiangsu Province Key Medical Discipline [ZDXKA2016020]
- Key Research and Development Program of Jiangsu Province of China [BE2016610]
- National Key Research and Development Program of China [2016YFC1300504]
- Young Talent Support Program for the China Stroke Association from the China Association for Science and Technology
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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.
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