Mechanism of hippocampal CRHR1 regulating chronic stress-induced learning and memory impairment in early aged mice
10.19405/j.cnki.issn1000-1492.2024.01.019
- Author:
Xinru Tu
1
;
Jiawen Xu
1
;
Rui Liu
1
;
Yulin Lu
2
;
Shu Wang
3
;
Yuyou Yao
1
,
4
Author Information
1. Dept of Health Inspection and Quarantine，School of Public Health，Anhui Medical University，Hefei 230032
2. The First Clinical Medical College，Anhui Medical University，Hefei 230032
3. Dept of Geriatrics，The Third Affiliated Hospital of Anhui Medical University，Hefei 230061
4. Anhui Provincial Key Laboratory of Population Health and Eugenics，Hefei 230032
- Publication Type:Journal Article
- Keywords:
chronic stress;
impairment of learning and memory;
CRHR1;
p-mTOR;
p-p70S6K
- From:
Acta Universitatis Medicinalis Anhui
2024;59(1):117-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective : To explore the mechanism of hippocampal corticotropin-releasing hormone ( CRH) receptor type 1 ( CRHR1 ) in chronic stress-induced learning and memory impairment in early aged mice．
Methods:C57BL /6J mice aged 12 －14 months were divided into two groups according to gender，and then divided into wild type (WT) group and hippocampal CRHR1 conditional gene knockout (KN) group according to genotype．Mice in each group were randomly divided into control group and stress group，and the stress group was subjected to chronic unpredictable stress ( CUS ) for 30 days． Genotyping of mice was performed using polymerase chain reaction ( PCR) ，agarose gel electrophoresis and real-time fluorescence quantitative PCR (RT-qPCR) ．The new object rec- ognition experiment and Morris Water maze measured learning and memory ability．Golgi-Cox staining was used to observe damage to hippocampal neuronal dendrites． The protein expressions of target protein of rapamycin (mTOR) ，p-mTOR (Ser2448) ，ribosomal protein S6 kinase ( p70S6K) and p-p70S6K ( Thr389 / Thr412 ) were detected by Western blot．Serum levels of corticotropin releasing hormone ( CRH) were measured by ELISA.
Results : Compared to mice without chronic stress，the cognitive coefficient of WT stress groups decreased after chron- ic stress，and the difference was statistically significant (P ＜0. 05) ，while there was no significant difference in cognitive coefficient of KN stress groups before and after chronic stress．Compared with the WT stress group，the escape latency of the WT control group was shortened (P＜0. 05) ，and the number of crossing the platform and tar- get quadrant increased (P ＜0. 01) ，and there was no significant difference in the KN groups above． Compared with the WT control group，the WT stress group had a significant reduction in the neuronal complexity in the hipp- ocampal CA1，CA3 and DG regions (P ＜0. 05) and significant reductions in the expression of p-mTOR and p- p70S6K in the hippocampus (P＜0. 05) ．There was no significant difference in the expression of p-mTOR between the KN stress group and the KN control group (P＞0. 05) ，except that the expression of p-mTOR in the hippocam- pus of the female group decreased (P＜0. 05) ．In addition，the serum level of CRH in the stress group was higher than that in the control group (P＜0. 01) ．
Conclusion :Hippocampal CRHR1 regulates learning and memory im- pairment and neuronal dendrite damage in early aged mice induced by chronic stress．The mechanism may be that high levels of CRH induced by chronic stress cannot bind to CRHR1 receptor，thereby enhancing the expression of down-regulated mTOR / p70S6K signaling pathway.
- Full text:202406241723116232海马CRHR1调节慢性应激...前期小鼠学习记忆损伤的机制_屠心茹.pdf
