Activation of M1 AChR regulates GluA1 and GluA2 to improve the memory impairment induced by plateau hypoxia in rats
10.16557/j.cnki.1000-7547.2024.06.006
- VernacularTitle:激活M1 AChR调控GluA1和GluA2改善高原低氧引起的大鼠记忆损伤
- Author:
Jiangpeng FENG
1
;
Lingquan HUANG
;
Quanyu YANG
;
Qing GA
;
Shenghua LI
;
Guoen JIN
Author Information
1. 青海大学医学部基础医学部,西宁 810016
- Publication Type:Journal Article
- Keywords:
plateau hypoxia;
learning and memory;
muscarinic acetylcholine receptor M1(M1 AChR);
ionotropic glutamate receptor AMPA type subunit 1(GluA1);
ionotropic glutamate receptor AMPA type subunit 2(Glu A2);
rat
- From:
Chinese Journal of Neuroanatomy
2024;40(6):703-712
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore whether the muscarinic acetylcholine receptor M1(M1 AChR)regulate the expression of ionotropic glutamate receptor AMP A type subunit 1(GluA1)and ionotropic glutamate receptor AMP A type subunit 2(GluA2),thus participating in the effects of plateau hypoxia on learning and memory in rats.Methods:Rats were randomly divided into normoxic group(Control),plateau hypoxia group(Hypoxia)and plateau hypoxia+TAK-071(an agonist of M1AChR)group.Morris water maze was utilized to detect the learning and memory ability of rats.Immunohistochemistry was utilized to determine the distribution and expression levels of M1 AChR,GluA1,and GluA2 in hippocampal CA1 and CA3 areas of rats.Western Blot was utilized to determine the expression levels of M1 AChR,GluA1,p-GluA1(Ser845),GluA2 and p-GluA2(Ser880)in hippocampus of rats.RT-qPCR was utilized to determine the mRNA expression levels of M1 AChR,GluA1,GluA2,ionotropic glutamate receptor NMDA type subunit 2A(NR2A),tau and amyloid β-protein(Aβ)in hippocampus of rats.Results:Plateau hypoxia could significantly increase the escape latency of rats in the spatial navigation test and shorten the stay time of rats in the target quadrant in the spatial probe test,while TAK-071 treatment could significantly improve the memory status of rats damaged by plateau hypoxia in the spatial probe test.There was a good correlation between the expression of GluA1,GluA2 and M1 AChR in CA1 and CA3 regions of hippocampus.In hippocampus,the expressions of GluA1 and GluA2 were synchro-nized with their corresponding phosphorylated proteins,and the correlativity between GluA1 and GluA2 and M1 AChR changed due to plateau hypoxia was reversed after TAK-071 treatment.TAK-071 could significantly reduce(P＜0.05)the expression levels of M1 AChR,GluA1,GluA2,NR2A,tau and Aβ mRNA increased due to plateau hypoxia.Conclusion:Activating M1 AChR can improve the memory impairment of rats caused by plateau hypoxia by regulating the expression of GluA1,GluA2 and their phosphorylated proteins.
