High-Altitude Hypoxia Triggers JNK Phosphorylation: A Molecular Switch Linking Hippocampal Energy Crisis, Neuronal Senescence, and Cognitive Impairment

Samples were collected at multiple time points using a chronic low-pressure hypoxia rat model (simulating an altitude of 6000m), covering: (1) epidemiological statistical data of 2819 populations in areas above 3000m altitude; (2) Western blot was used to detect the expression and phosphorylation levels of JNK/p53/Bim and other proteins; (3) LC-MS/MS untargeted metabolomics analysis; (4) Immunofluorescence staining (LAMP1/COVIV and PHD2/HIF-2 α); (5) Observation of transmission electron microscopy ultrastructure; (6) Morris water maze spatial memory test; (7) Morphological analysis of hippocampal CA1 region using HE staining.

Statistical analysis was conducted using GraphPad Prism 10.1 for multiple sample comparisons (t-test/U-test/ANOVA/Kruskal Wallis et al.), while metabolomics was processed using MSDIAL 4.9 and differential metabolites were screened using Wilcoxon/ANOVA combined with VIP>1 and FC ≥ 1.5 (FDR corrected p<0.05). The dataset is shared using CC BY 4.0 protocol.