Prenatal ethanol exposure-induced hypothalamic an imbalance of glutamatergic/GABAergic projections and low functional expression in male offspring rats
This study was designed to demonstrate that prenatal ethanol exposure (PEE) can induce low functional expression of the hypothalamus in male offspring rats and explore the underlying mechanism. Pregnant rats were administered 4 g/kg ethanol or normal saline by oral gavage each day from gestational d...
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Veröffentlicht in: | Food and chemical toxicology 2020-07, Vol.141, p.111419, Article 111419 |
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Zusammenfassung: | This study was designed to demonstrate that prenatal ethanol exposure (PEE) can induce low functional expression of the hypothalamus in male offspring rats and explore the underlying mechanism. Pregnant rats were administered 4 g/kg ethanol or normal saline by oral gavage each day from gestational day (GD) 9 to GD20. Male GD20 foetuses and postnatal day 120 adult offspring rats were sacrificed under anaesthesia. Hypothalamic cells from male GD20~postnatal day (PD) 7 rats were treated with different doses of corticosterone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. In this study, we found that PEE-induced overexposure of maternal glucocorticoids enhanced the expression of L-glutamic acid decarboxylase (GAD) 67 in the hypothalamic paraventricular nucleus (PVN) by activating the glucocorticoid metabolic activation system, further inducing the conversion of glutamate to L-gamma-aminobutyric acid (GABA) and developmental imbalance of glutamatergic/GABAergic projections to the PVN. The imbalance change was maintained until after birth, resulting in the inhibition of parvocellular neurons and low functional expression of the hypothalamus in PEE offspring rats. Our study indicated that low functional expression of the hypothalamus in male PEE offspring rats was associated with developmental programming of an imbalance of glutamatergic/GABAergic projections to the PVN.
•PEE induced activation of the hypothalamic glucocorticoid metabolic activation system of 11βHSDs/GR/C/EBPa.•PEE induced the upregulation of hypothalamic GAD67 expression by activating GR.•Enhanced expression of hypothalamic GAD67 led to a developmental imbalance of glutamatergic/GABAergic projections to the PVN.•The imbalance of glutamatergic/GABAergic projections mediated hypothalamic low functional expression in male offspring rats. |
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ISSN: | 0278-6915 1873-6351 |
DOI: | 10.1016/j.fct.2020.111419 |