Prenatal ethanol exposure-induced hypothalamic an imbalance of glutamatergic/GABAergic projections and low functional expression in male offspring rats
Prenatal ethanol exposure-induced hypothalamic an imbalance of glutamatergic/GABAergic projections and low functional expression in male offspring rats
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产前乙醇暴露诱导雄性子代大鼠下丘脑谷氨酸能/GABA能投射失衡和低功能表达
DOI：
10.1016/j.fct.2020.111419
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发表时间：
2020
影响因子：
4.3
通讯作者：
Wang Hui
中科院分区：
文献类型：
--
作者：
Lu Juan;Li Qiang;Ma Guoqin;Hong Chenghao;Zhang Wenqian;Wang Yuxia;Wang Hui
本研究旨在证明孕期酒精暴露(PEE)可导致雄性子代大鼠下丘脑功能表达降低，并探讨其可能机制。孕鼠从妊娠第9天至第20天，每天经口灌胃4 mg/kg乙醇或生理盐水。雄性GD20胎鼠和出生后120只成年子代大鼠在麻醉下处死。用不同剂量的皮质酮和糖皮质激素受体(GR)拮抗剂米非司酮处理GD20~出生后7天雄性大鼠下丘脑细胞5d。在本研究中，我们发现，PEE诱导的母体糖皮质激素过度暴露通过激活糖皮质激素代谢激活系统，促进下丘脑室旁核L-谷氨酸脱羧酶67的表达，进而诱导谷氨酸向L-γ-氨基丁酸的转化，并导致谷氨酸/GABA能投射向室旁核的发育失衡。这种失衡的变化一直持续到出生后，导致PEE子代大鼠小细胞神经元受到抑制，下丘脑功能表达降低。我们的研究表明，雄性PIE子代大鼠下丘脑功能表达的降低与谷氨酸/GABA能投射到下丘脑室旁核的不平衡的发育编程有关。
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.