Deficit of RACK1 contributes to the spatial memory impairment via upregulating BECLIN1 to induce autophagy

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• 作者：Jiejun Zhu^a ; ^b ; ^{506157549@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Xu Chen^c ; ^{chenxu99@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Yun Song^d ; ^{songyunjn@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yuanyuan Zhang^a ; ^b ; ^{sarahyyzhang@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Liming Zhou^a ; ^b ; ^{zhou108@163.com" class="auth_mail" title="E-mail the corresponding author} ; Lihong Wan^a ; ^b ; ^{wanlihong1976@sina.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Learning and memory ; RACK1 ; BECLIN1 ; LC3
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：151
• 期：Complete
• 页码：115-121
• 全文大小：1566 K

文摘

Deficiency of activated C kinase1 (RACK1) in the brain of aging animal and Alzheimer's disease was characterized by cognitive dementia and spatial memory impairment. However, the correlation between the RACK1 and spatial memory impairment and the mechanism involved in it remains unknown.

Main methods

Spatial memory impairment was performed in mice by lateral ventricle injection of Aβ_25–35 (n = 16, 10 μl) and intraperitoneal injection of scopolamine (n = 16, 10 ml/kg). After the Morris water maze (MWM) which was performed to determine the ability of learning and memory in mice, expression of RACK1 was tested and the damage of hippocampus was confirmed by histopathology test. ShRACK1 was then used to decrease the level of RACK1 in hippocampus to test the ability of learning and memory and histopathology changes in hippocampus. To look into the mechanism of RACK1 on spatial memory impairment, we further measured the expression of autophagy proteins BECLIN1 and LC3-II/I in hippocampus of all mice.

Key findings

Both the Aβ_25–35, scopolamine impaired the spatial memory in mice (for escape latency, P = 0.0004, P < 0.0001) and severely damaged hippocampal DG neurons (P = 0.012, P = 0.014). The expression of RACK1 was significantly decreased which was concomitant with elevated BECLIN1 and LC3-II/I (P < 0.001). Suppression of RACK1 by ShRACK1 plasmid (shGnb2l1) significantly impaired the spatial memory in mice, damaged hippocampal DG neurons (P = 0.013), and increased the proteins of BECLIN1 and LC3-II/I (P < 0.005).

Significance

It demonstrated that the deficit of RACK1 in hippocampus impairs the ability of learning and memory in mice via up regulating autophagy.