Inhibition of progesterone receptor membrane component-1 exacerbates neonatal hypoxic-ischemic cerebral damage in male mice

• Published in: Experimental neurology 2022-01, Vol.347, p.113893-113893, Article 113893
• Main Authors: Sun, Xiaoyu, Hu, Yuting, Zhou, Hui, Wang, Shang, Zhou, Chao, Lin, Li, Zhu, Taiyang, Ge, Ji, Han, Jingjing, Zhou, Yan, Jin, Guoliang, Wang, Yuqiao, Zu, Jie, Shi, Hongjuan, Yang, Xingxing, Zan, Kun, Wang, Jun, Hua, Fang
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Female; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - pathology; Hypoxic-ischemic cerebral injury; Male; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Neonatal; Neurological function; Pgrmc1; Receptors, Progesterone - metabolism; Sex Characteristics; Signal Transduction - physiology; Signaling pathway
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2021.113893

This study investigated the expression of progesterone receptor membrane component 1 (pgrmc1) in the brains of male and female mice, and the effect of inhibiting pgrmc1 on neonatal hypoxic–ischemic (HI) cerebral injury in male mice. A mouse model of neonatal HI brain injury was established, and AG205, a specific antagonist of pgrmc1, was injected into the left lateral cerebral ventricle 1 h before HI. Histological staining, behavior testing, Western blots, and quantitative PCR (qPCR) were employed to evaluate pgrmc1 expression, brain damage, neurological function, and molecular mechanisms. Results demonstrated that the mRNA and protein levels of pgrmc1 increased significantly in the cortex and hippocampus 72 h after HI without sex differences. The inhibition of pgrmc1 exacerbated the neonatal brain damage in the acute stage of HI in male mice as seen in the increase in brain water content, infarction area, and neuronal death. Inhibition of pgrmc1 also aggravated the neurological dysfunction and anxiety induced by HI brain injury. In addition, inhibition of pgrmc1 activated the NF-kB signaling and NF-κB-mediated cytokines, and inhibited BDNF/PI3K/AKT pathway in the brains of the newborn HI mice. The results indicated that pgrmc1 inhibition exacerbated the brain damage in newborn male mice subjected to HI by activating IκBα/NFκB signaling and inhibiting BDNF/PI3K/Akt pathway. •Expression of pgrmc1 increases in neonatal mouse brain after hypoxic/ischemic (HI) injury.•Inhibition of pgrmc1 exacerbates the neonatal brain damage in the acute stage of HI cerebral injury in male mice.•Blocking pgrmc1 activates NF-kB signaling and inhibits BDNF/PI3K/AKT pathway in neonatal male mice brain.