Whole transcriptome sequencing of a 24-hour restraint stress mouse model treated with hypoxic preconditioning

Depression, a neurological disorder triggered by stressful stimuli like hypoxia, is associated with high morbidity and mortality. Hypoxic preconditioning (HPC) is an endogenous mechanism that upregulates BDNF, an marker of depression, to elicit neuroprotective effects in recent research. However, the preventive mechanisms of HPC against depression remain poorly understood. Therefore, this study aimed to investigate the effect and regulatory mechanisms of HPC on depressive behaviors via BDNF signaling. Initially, ICR mice were subjected to HPC followed by establishment of a 24-hour restraint stress model to mimic depressive behaviors. Subsequent analysis focused on changes in depressive behaviors, biochemical markers, BDNF signaling and its modulation of synaptic structure and neurogenesis. Furthermore, whole transcriptome sequencing was conducted. The results indicated that HPC relieved characteristic depressive behaviors in restraint stress model mice, redressed levels of neurotransmitter and elevated antioxidant status, upregulated the BDNF signaling in the hippocampus. The PSD-95, number and complexity of neuronal dendritic spines, and hippocampal neurogenesis in model mice were enhanced by HPC. Restraint stress regulated 373 DElncRNAs, 166 DEcircRNAs, 29 DEmiRNAs and 1235 DEmRNAs, which were also modulated by HPC. The ceRNA networks were constructed based on these DERNAs. Functional enrichment analysis revealed that it related to synapses, neurogenesis and Neurotrophin signaling. These results suggested that HPC upregulated BDNF and activated the BDNF signaling to improve synaptic deficits and hippocampal neurogenesis, ultimately ameliorated depressive behaviors in mice. The identification of various mRNAs and ncRNAs and their constituent ceRNAs provides theoretical guidance for the clinical treatment of depression with HPC.