[Effects of miR‑17‑5p regulation of the HIF‑1α/BNIP3 pathway on cognitive function and hippocampal synaptic plasticity in epileptic mice].
Year: 2026
Type: article
Abstract: OBJECTIVES: To investigate the effects of microRNA (miR)-17-5p regulation of the hypoxia-inducible factor-1α (HIF-1α)/Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) pathway on cognitive function and hippocampal synaptic plasticity in epileptic mice. METHODS: =12 each): normal control, PTZ, miR‑17‑5p agomir control (PTZ + agomir negative control), miR‑17‑5p agomir (PTZ + miR‑17‑5p agomir), miR‑17‑5p agomir + pcDNA (PTZ + miR‑17‑5p agomir + empty vector), miR‑17‑5p agomir + pc-HIF‑1α (PTZ + miR‑17‑5p agomir + HIF‑1α overexpression plasmid), and miR‑17‑5p agomir + pc-BNIP3 (PTZ + miR‑17‑5p agomir + BNIP3 overexpression plasmid). Cognitive function was evaluated by the Morris water maze test. Field potential recording was used to measure field excitatory postsynaptic potentials (fEPSPs) in the hippocampal CA1 region. Transmission electron microscopy was used to observe synaptic ultrastructure. Quantitative real-time reverse transcription polymerase chain reaction and Western blot were employed to detect miR‑17‑5p, HIF‑1α, BNIP3, and synapse-related proteins [postsynaptic density protein 95 (PSD95), synaptotagmin-1 (Syt1), synaptosome-associated protein 25 (SNAP25), and gephyrin] in the hippocampus. A dual-luciferase reporter assay was used to verify whether miR-17-5p directly targets HIF-1α. RESULTS: <0.05). The dual-luciferase assay confirmed that miR‑17‑5p could directly bind to the 3'-UTR of HIF‑1α. CONCLUSIONS: miR‑17‑5p can directly target and inhibit the HIF‑1α/BNIP3 pathway, upregulate the expression of synapse-related proteins, repair hippocampal synaptic ultrastructure, enhance synaptic plasticity, and thereby improve cognitive function in epileptic mice, providing a potential therapeutic target for epilepsy-related cognitive impairment.
Source: PubMed Central
Authors: Jin-Lai Zhang, Pei-Pei Gao, Yu Ren
Institution: Cangzhou Central Hospital
Language: Chinese
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223218547
