Effect of Lnc001209 in regulating the PI3K/AKT/mTOR pathway on Aβ clearance in aluminum-induced cognitive impairment
Objective To investigate the mechanism of Lnc001209 and phosphoinositide 3-kinase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),and amyloid β-protein(Aβ)in aluminum-induced cognitive impairment.Methods Specific pathogen free adult male SD rats were randomly divided into control group,empty vector group,adeno-associated virus(AAV)group,aluminum maltolate(Al-maltolate)group,and AAV+Al-maltolate group,with 10 rats in each group.AAV and AAV+Al-maltolate group rats were injected with 5 μL of AAV overexpressing Lnc001209 with a titer of 1× 1012 vg/mL into the lateral ventricle using stereotaxic coordinates.Empty vector group rats were injected with 5 μL of empty vector AAV with a titer of 1×1012 vg/mL into the lateral ventricle using stereotaxic coordinates.Control and Al-maltolate group rats underwent the same surgical procedure without any injections.The rats were intraperitoneally injected at the volume of 1 mL/kg body weight after 14 days of single cage feeding.Rats in the Al-maltolate group and AAV+Al-maltolate group were treated with 20 μmol/kg body weight Al-maltolate,while rats in the control group,empty vector group and AAV group were treated with an equivalent volume of 0.9％sodium chloride solution every other day for three months.The Morris water maze test was used to detect the learning and memory abilities of rats after treatment.The hippocampal tissues of the rats were collected to detect the expression of Aβ using the enzyme-linked immunosorbent assay and to detect the expression of microtubule-associated protein 1 light chain 3B(LC3B)using immunofluorescence.Western blot was used to detect the expression of phosphat idylinositol 3-kinase(PI3K),protein kinase B(AKT),mammalian target of rap amycin(mTOR),and their corresponding phosphorylated proteins,and reverse transcription-polymerase chain reaction was used to detect the expression of Lnc001209.Results ⅰ)Compared with the rats in control group,the escape latencies of rats in the Al-maltolate group were longer from the second day of Morris water maze experiment(all P＜0.05),the relative expression of Aβ40,Aβ42,phosphorylated PI3K(p-PI3K),phosphorylated AKT(p-AKT)and phosphorylated mTOR(p-mTOR)proteins increased in the hippocampal tissues(all P＜0.05),the average fluorescence intensity of LC3B and the relative expression of PI3K,AKT and mTOR proteins decreased(all P＜0.05),the relative expression of Lnc001209 decreased(P＜0.05).ⅱ)Compared with the rats in Al-maltolate group,the escape latencies of rats in AAV+Al-maltolate group were shortened from the second day of Morris water maze experiment(all P＜0.05),and the relative expression of Aβ40,Aβ42,p-PI3K,p-AKT and p-mTOR proteins in hippocampus decreased(all P＜0.05),the average fluorescence intensity of LC3B and the relative expression of PI3K,AKT and mTOR proteins increased(all P＜0.05),the relative expression of Lnc001209 increased(P＜0.05).Conclusion Aluminum can affect the PI3K/AKT/mTOR protein signaling pathway through Lnc001209,leading to an increase in Aβ and a decrease in neuronal autophagy,ultimately resulting in cognitive impairment.
AluminumLearning and memoryLong non-coding RNAPhosphoinositide 3-kinaseProtein kinase BMammalian target of rapamycinAmyloid β-proteinMicrotubule-associated protein 1 light chain 3B
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