Sex and the Estrous-Cycle Phase Influence the Expression of G Protein-Coupled Estrogen Receptor 1 (GPER) in Schizophrenia: Translational Evidence for a New Target.

Autor: da Silva FER; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1000, 60430-275, CE, Fortaleza, Brazil., Cordeiro RC; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1000, 60430-275, CE, Fortaleza, Brazil.; University of Texas Health Science Center at Houston, Houston, USA., de Carvalho Lima CN; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1000, 60430-275, CE, Fortaleza, Brazil.; University of Texas Health Science Center at Houston, Houston, USA., Cardozo PL; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Vasconcelos GS; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1000, 60430-275, CE, Fortaleza, Brazil., Monte AS; Health Science Institute, University of International Integration of Afro-Brazilian Lusophony UNILAB, Redenção, Brazil., Sanders LLO; Course of Medicine, Centro Universitário Christus-Unichristus, Fortaleza, Brazil.; Department of Clinical Medicine, Federal University of Ceara, Fortaleza, Brazil., Vasconcelos SMM; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1000, 60430-275, CE, Fortaleza, Brazil., de Lucena DF; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1000, 60430-275, CE, Fortaleza, Brazil., Cruz BF; Department of Mental Health, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Nicolato R; Department of Mental Health, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Seeman MV; Department of Psychiatry, University of Toronto, Toronto, Canada., Ribeiro FM; Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Macedo DS; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1000, 60430-275, CE, Fortaleza, Brazil. danielle.macedo@ufc.br.; National Institute for Translational Medicine (INCT-TM, CNPq), São Paulo, Brazil. danielle.macedo@ufc.br.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2023 Jul; Vol. 60 (7), pp. 3650-3663. Date of Electronic Publication: 2023 Mar 14.
DOI: 10.1007/s12035-023-03295-x
Abstrakt: Schizophrenia is a mental disorder with sex bias in disease onset and symptom severity. Recently, it was observed that females present more severe symptoms in the perimenstrual phase of the menstrual cycle. The administration of estrogen also alleviates schizophrenia symptoms. Despite this, little is known about symptom fluctuation over the menstrual cycle and the underlying mechanisms. To address this issue, we worked with the two-hit schizophrenia animal model induced by neonatal exposure to a virus-like particle, Poly I:C, associated with peripubertal unpredictable stress exposure. Prepulse inhibition of the startle reflex (PPI) in male and female mice was considered analogous to human schizophrenia-like behavior. Female mice were studied in the proestrus (high-estrogen estrous cycle phase) and diestrus (low-estrogen phase). Additionally, we evaluated the hippocampal mRNA expression of estrogen synthesis proteins; TSPO and aromatase; and estrogen receptors ERα, ERβ, and GPER. We also collected peripheral blood mononuclear cells (PBMCs) from male and female patients with schizophrenia and converted them to induced microglia-like cells (iMGs) to evaluate the expression of GPER. We observed raised hippocampal expression of GPER in two-hit female mice at the proestrus phase without PPI deficits and higher levels of proteins related to estrogen synthesis, TSPO, and aromatase. In contrast, two-hit adult males with PPI deficits presented lower hippocampal mRNA expression of TSPO, aromatase, and GPER. iMGs from male and female patients with schizophrenia showed lower mRNA expression of GPER than controls. Therefore, our results suggest that GPER alterations constitute an underlying mechanism for sex influence in schizophrenia.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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