Overexpression Of SFPQ Improves Cognitive Memory Of AD Model Mice And Its Mechanism

Objective(s):Alzheimer’s disease(AD)is a kind of neurodegenerative disease with great influence,and its pathogenesis is numerous and complex,so it has been explored but there is still no good treatment method.Our previous studies have found that SFPQ may have antioxidant functions.Therefore,this study took SFPQ(splicing factor rich in proline and glutamine)as the principal variable to explore its influence on the behavior and pathology of AD model mice induced by Aβ1-42,and further explored and analyzed the deep mechanism,so as to provide molecular targets for the treatment of AD.This is the first time to explore the mechanism of SFPQ directly expressed in the hippocampus of AD mice.Methods:(1)The mouse model of Alzheimer’s disease was made by injection of Aβ1-42 into the lateral ventricle,and the model was successfully established 14 days later by using the new object,Y maze and open field experiments.(2)The mice were divided into two groups:(1)Vector group;(2)Overexpressing SFPQ group(AAV-SFPQ);Vector and AAV-SFPQ were injected on both sides of the hippocampus of mice,each at 1ul.(3)Three weeks after virus injection,cognition and memory of mice were tested by behavioral test,and bilateral hippocampal tissues of mice in each group were collected.Immunofluorescence showed that the overexpression of SFPQ in hippocampus was successful and the overexpressed SFPQ was mainly located in neurons.Western Blot was used to detect SFPQ,antioxidation-related proteins GST,HO-1,AD-related marker protein APP,Tau,synaptic and memory related proteins p-CREB,PSD95,apoptosis-related Bcl-2,Bax,and signaling pathways related p-PI3K/PI3 K,p-AKT /AKT protein expression level;HE staining was used to observe the histopathological changes in the hippocampus before and after virus injection.Nissner’s corpuscles were observed by Nissner’s staining.Results:(1)AD mouse model was successfully established by Aβ1-42 after verification by behavioral new objects,Y maze and open field experiments;(2)Behavioral novel objects,Y maze,open field experiment,Western Blot,and immunofluorescence jointly confirmed that adeno-associated viruses overexpressed SFPQ in hippocampal CA1,CA2 and CA3;(3)After overexpression of SFPQ,the cognition and memory of AD model mice were significantly improved,and the AD-related marker proteins APP and Tau decreased,the expression of antioxidant enzymes GST and HO-1 in hippocampal tissues was up-regulated,and the anti-apoptotic protein Bcl-2/Bax was upregulated;(4)After overexpression of SFPQ,the expression of synapse-related protein PSD95 and memory-related protein p-CREB in AD model mice was up-regulated;(5)After overexpression of SFPQ,the expression of p-PI3K/PI3 K and p-AKT/AKT in hippocampal tissues of AD model mice was up-regulated;Conclusion(s):(1)Hippocampal overexpression of SFPQ can significantly improve the cognitive and memory ability of AD mice.(2)Overexpression of SFPQ in hippocampus can up-regulate the antioxidant enzymes GST and HO-1,down-regulate APP and Tau,enhance the anti-apoptotic ability of neurons,up-regulate p-CREB and PSD95 protein,and activate PI3K/AKT pathway.By activating PI3K/AKT pathway,SFPQ may up-regulate the antioxidant enzyme system,down-regulate the pathological proteins related to AD,enhance the anti-apoptosis ability of neurons,improve the prominent function and long-term enhancement effect,so as to improve the cognitive and memory ability of AD mice.(3)SFPQ may be an important potential molecular target for AD.