HIF-1A regulates cognitive deficits of post-stroke depressive rats

• Published in: Behavioural brain research Vol. 458; p. 114685
• Main Authors: Tan, Yafu, Yu, Yongjia, Liao, Xingsheng, Yu, Liang, Lai, Haiyan, Li, Xiuchan, Wang, Chunxi, Wu, Song, Feng, Daqing, Liu, Chang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 26.02.2024
• Subjects: Animals; Cognition; Cognitive dysfunction; Cognitive Dysfunction - complications; Depression; HIF-1A; Hypoxia-Inducible Factor 1, alpha Subunit; MicroRNAs - metabolism; NBR1; Rats; Stroke; Stroke - complications; Depression; Stroke; HIF-1A; Cognitive dysfunction; NBR1
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2023.114685

Post-stroke depression (PSD) is a serious neuropsychiatric complication post stroke and leads to cognitive deficits. This study was conducted to explore the molecular mechanism of hypoxia-inducible factor-1α (HIF-1A) in cognitive dysfunction in rats with PSD. The rat model of PSD was established by middle cerebral artery occlusion, followed by 3 weeks of treatment with chronic unpredictable mild stress. The levels of miR-582-5p, HIF-1A, and neighbor of Brca1 gene (NBR1) in brain tissues were determined using RT-qPCR. The behaviors and cognitive capacity of rats were evaluated by various behavioral tests. PSD rats were injected with HIF-1A/miR-582-5p lowexpression vectors or NBR1 overexpression vectors via stereotactic method. The binding of HIF-1A to NBR1 or miR-582-5p was analyzed by chromatin immunoprecipitation and dual-luciferase assay. HIF-1A and NBR1 were highly expressed while miR-582-5p was poorly expressed in the brain of PSD rats. HIF-1A inhibition alleviated cognitive dysfunction of PSD rats. miR-582-5p was the upstream miRNA of HIF-1A, and HIF-1A specifically interacted with the NBR1 promoter to enhance NBR1 expression. miR-582-5p downregulation and NBR1 upregulation reversed the alleviative role of HIF-1A inhibition in cognitive dysfunction of PSD rats. In summary, HIF-1A inhibition may be a therapeutic target for cognitive dysfunction post PSD.