G protein-coupled estrogen receptor 1 deficiency impairs adult hippocampal neurogenesis in mice with schizophrenia

• Published in: Journal of chemical neuroanatomy 2023-10, Vol.132, p.102319, Article 102319
• Main Authors: Zhang, Chun, Niu, Jian-Guo, Kong, Xue-Rui, Mi, Xiao-Juan, Liu, Qiang, Chen, Fei-Fei, Rong, Wei-Fang, Liu, Juan
• Format: Article
• Language: English
• Subjects: Adult hippocampal neurogenesis; Cognitive impairment; Dizocilpine maleate; G protein-coupled estrogen receptor 1; Schizophrenia
• ISSN: 0891-0618; 1873-6300; 1873-6300
• DOI: 10.1016/j.jchemneu.2023.102319

This study aimed to confirm that G protein-coupled estrogen receptor 1 (GPER1) deficiency affects cognitive function by reducing hippocampal neurogenesis via the PKA/ERK/IGF-I signaling pathway in mice with schizophrenia (SZ). Mice were divided into four groups, namely, KO Con, WT Con, KO Con, and WT SZ (n = 12 in each group). All mice were accustomed to the behavioral equipment overnight in the testing service room. The experimental conditions were consistent with those in the animal house. Forced swimming test and Y-maze test were conducted. Neuronal differentiation and maturation were detected using immunofluorescence and confocal imaging. The protein in the PKA/ERK/IGF-I signaling pathway was tested using Western blot analysis. GPER1 KO aggravated depression during forced swimming test and decreased cognitive ability during Y-maze test in the mouse model of dizocilpine maleate (MK-801)-induced SZ. Immunofluorescence and confocal imaging results demonstrated that GPER1 knockout reduced adult hippocampal dentate gyrus neurogenesis. Furthermore, GPER1-KO aggravated the hippocampal damage induced by MK-801 in mice through the PKA/ERK/IGF-I signaling pathway. GPER1 deficiency reduced adult hippocampal neurogenesis and neuron survival by regulating the PKA/ERK/IGF-I signaling pathway in the MK-801-induced mouse model of SZ. •GPER1 deficiency further reduces newborn hippocampal neurons and decreases hippocampal neurogenesis in the SZ mice.•GPER1 is involved in SZ possibly via the hypoactive PKA/ERK/IGF-I signaling pathway in the hippocampus of GPER1-deficient mice.•This report provides evidence of the association between GPER1 and SZ in experimental animals.