A Preliminary Study Of The Effects And Related Mechanisms Of SGK1 Overexpression On The Spatial Learning And Memory In APP/PS1 Mice

Objective The increasing occurrence and ineffective treatment of Alzheimer’s disease has become one of the major challenges of the whole world.Limited studies have shown that serum-and glucocorticoid-inducible kinase 1(SGK1)is involved spatial memory formation and consolidation,but its role in AD-specific spatial memory impairment and the related mechanisms are not clear.In this study,we explored the role and related mechanisms of SGK1 overexpression on spatial learning and memory,hippocampal β-amyloid(Aβ)pathology and neuroplasticity in middle-aged female APP/PS1 transgenetic AD model mice.Method In this study,firstly we examined the expression of SGK1 in hippocampus of 4-,6-,8-,10-month-old female APP/PS1 mice by qPCR and immunohistochemistry.Based on the findings,SGK1-overexpressing AAV(oSGK1)was constructed.The mice were randomly divided into C57 group(C57),APP/PS1 mice injected with empty virus vector group(APP/PS1)and APP/PS1 mice injected with overexpressed SGK1 virus group(oSGK1).qPCR and immunofluorescence staining were used to determine whether the AAV vector was successfully constructed;behavior changes were measured by Morris water maze test;Congo red staining,immunohistochemistry and immunofluorescence staining were used to examine Aβ production and its deposit(senile plaques).The density of CA1 dendritic spines was examined with Golgi staining;Western blot was used to detect the expression of AD pathology-related proteins,synaptic proteins and actin cytoskeleton remodeling proteins.Results 1 Age-related changes of hippocampal SGK1 in the AD Mice: there were no significant differences among 4,6 and 8 M(p>0.05),but the levels of hippocampal SGK1 were significantly decreased at 10 M when compared with other checkpoint.2 AAV vector verification and Morris water maze: qPCR and immunofluorescence staining results showed that the overexpressed SGK1 virus was effectively constructed.The results of Morris water maze showed that while the learning abilities of the AD mice were not statistically improved;the impaired spatial memory of AD mice was significantly ameliorated after SGK1 overexpression.3 Congo red staining,immunohistochemistry and immunofluorescence: SGK1 overexpression induced decrease Aβ production and senile plaques deposit.4 Golgi-Staining: the spine density was significantly decreased in the hippocampus of APP/PS1 mice and this decr ease could be reversed by oSGK1 treatment.5 Western blot: Overexpression of SGK1 induced significant changes in Aβ-related proteins,synaptic proteins and actin remodeling proteins.Conclusion 1 At the age of 10 M,the spatial learning and memory of AD mice was significantly decreased,the expression of hippocampal SGK1 was significantly decreased,the generation of Aβ and its deposition(senile plaques)were significantly increased,and the level of synaptic proteins and actin polymerization remodeling proteins were significantly changed.2 In AD mice,hippocampus-specific overexpression SGK1 could ameliorate spatial memory inhibit the production and deposit of Aβ,upregulate CA1 spine density,increase synaptic proteins and actin polymerization related proteins.3 Overexpression of SGK1 may improve spatial learning and memory in AD mice by acting on production and deposit of Aβ,the density of CA1 dendritic spines,the level of synaptic proteins as well as actin polymerization.