Impact of Gestational Haloperidol Exposure on miR-137-3p and Nr3c1 mRNA Expression in Hippocampus of Offspring Mice.

Int J Neuropsychopharmacol 2022

Yoshino Y, Kumon H, Shimokawa T

Abstract

  1. Int J Neuropsychopharmacol. 2022 Oct 25;25(10):853-862. doi: 10.1093/ijnp/pyac044.

Impact of Gestational Haloperidol Exposure on miR-137-3p and Nr3c1 mRNA Expression in Hippocampus of Offspring Mice.

Yoshino Y(1), Kumon H(1), Shimokawa T(2), Yano H(3), Ochi S(1), Funahashi Y(1), Iga JI(1), Matsuda S(2), Tanaka J(3), Ueno SI(1).

Author information: (1)Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan. (2)Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. (3)Department of Molecular and Cellular Physiology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

BACKGROUND: Schizophrenia is a mental disorder caused by both environmental and genetic factors. Prenatal exposure to antipsychotics, an environmental factor for the fetal brain, induces apoptotic neurodegeneration and cognitive impairment of offspring similar to schizophrenia. The aim was to investigate molecular biological changes in the fetal hippocampus exposed to haloperidol (HAL) by RNA expression as a model of the disorder. METHODS: HAL (1 mg/kg/d) was administered to pregnant mice. Upregulated and downregulated gene expressions in the hippocampus of offspring were studied with RNA-sequencing and validated with the qPCR method, and micro-RNA (miR) regulating mRNA expressional changes was predicted by in silico analysis. An in vitro experiment was used to identify the miRNA using a dual-luciferase assay. RESULTS: There were significant gene expressional changes (1370 upregulated and 1260 downregulated genes) in the HAL group compared with the control group on RNA-sequencing analysis (P < .05 and q < 0.05). Of them, the increase of Nr3c1 mRNA expression was successfully validated, and in silico analysis predicted that microRNA-137-3p (miR-137-3p) possibly regulates that gene’s expression. The expression of miR-137-3p in the hippoca

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