The p38 MAPK signaling pathway mediates the reduction of apoptosis,inflammation and oxidative stress levels in AD mice by cerebroprotein
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-β142.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 Aβgroup 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.
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