The p38 MAPK signaling pathway mediates the reduction of apoptosis, inflammation and oxidative stress levels in AD mice by cerebroprotein

doi:10.3969/j.issn.1006-7795.2024.06.016

Abstract

Abstract: Objective Our objective was to examine the potential of cerebroprotein hydrolysate for injection I (CH-I) in mitigating oxidative stress, apoptosis, and neuroinflammation in an Alzheimer's disease (AD) model, while also gaining a better understanding of the underlying mechanisms. Methods AD mouse model was established through the intrahippocampal injection of amyloid-β_1-42. The experiment consisted of four groups: Control (Con) group, Aβ group, Aβ+CH-I group, and CH-I group. The learning and memory abilities of the mice were assessed using the new object recognition experiment and Y-maze. Enzyme-linked immunosorbent assay was employed to measure the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thioredoxin, and catalase (CAT) in brain tissue. Additionally, Tunel staining was utilized to evaluate the levels of cell apoptosis. Aβ group and Aβ+CH-I group were extracted for RNA-seq and bioinformatics analysis and verification.Western blotting analysis was conducted to detect proteins associated with the pathway ［c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), p38 MAPK］. Results In comparison to the Con group and the Aβ+CH-I group, the Aβ group exhibited a significant decrease in the proportion of time allocated to exploring novel arms/objects. Moreover, the Aβ group displayed significantly lower levels of SOD and GSH-Px activities in mice, in contrast to both the Con group and the Aβ+CH-I group, with statistically significant distinctions. The RNA-seq analysis demonstrated a significant downregulation of the MAPK signaling pathway in the Aβ+CH-I group compared to the Aβ group. Additionally, the Aβ+CH-I group exhibited noteworthy reductions in apoptosis levels, p38 MAPK protein, and inflammation levels when compared to the Aβ group. Conclusions CH-I exerts neuroprotective effects through the modulation of the p38 MAPK signaling pathway, thereby conferring neuronal resistance against oxidative stress and apoptosis.

Key words: Alzheimer's disease, p38 MAPK, CH-I, oxidative, apoptosis, inflammation

CLC Number:

R741

Gou Dongyun, Liang Jiayi, Guo Ziyu, Yan Fangyuan, Wang Shuaixiang , Qu Shuo, Gao Yan, Zhang Yujia, Ma Xiaowei. The p38 MAPK signaling pathway mediates the reduction of apoptosis, inflammation and oxidative stress levels in AD mice by cerebroprotein[J]. Journal of Capital Medical University, 2024, 45(6): 1062-1070.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2024.06.016

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2024/V45/I6/1062

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