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

Abstract

AimsDeficiency 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 methodsSpatial memory impairment was performed in mice by lateral ventricle injection of Aβ25–35 (n=16, 10μl) and intraperitoneal injection of scopolamine (n=16, 10ml/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 findingsBoth the Aβ25–35, 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). SignificanceIt demonstrated that the deficit of RACK1 in hippocampus impairs the ability of learning and memory in mice via up regulating autophagy.