Impact of Gestational Haloperidol Exposure on miR-137-3p and Nr3c1 mRNA Expression in Hippocampus of Offspring Mice.
Int J Neuropsychopharmacol
; 25(10): 853-862, 2022 10 25.
Article
en En
| MEDLINE
| ID: mdl-35859315
ABSTRACT
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 hippocampus of offspring was significantly decreased in the first generation, but it increased in the second generation. In vitro experiments with Neuro2a cells showed that miR-137-3p inversely regulated Nr3c1 mRNA expression, which was upregulated in the HAL group.CONCLUSIONS:
These findings will be key for understanding the impact of the molecular biological effects of antipsychotics on the fetal brain.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antipsicóticos
/
MicroARNs
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Int J Neuropsychopharmacol
Asunto de la revista:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón