Neonatal di-(2-ethylhexyl)phthalate exposure induces permanent alterations in secretory CRH neuron characteristics in the hypothalamus paraventricular region of adult male rats
Neonatal di-(2-ethylhexyl)phthalate exposure induces permanent alterations in secretory CRH neuron characteristics in the hypothalamus paraventricular region of adult male rats
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DOI：
10.1016/j.expneurol.2023.114616
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发表时间：
2023-11-30
影响因子：
5.3
通讯作者：
Fan，Pei
中科院分区：
文献类型：
--
作者：
Li，Li;Su，Ying;Fan，Pei
下丘脑室旁核（PVN）内的促肾上腺皮质激素释放激素（CRH）神经元在调节下丘脑-垂体-肾上腺（HPA）轴中起重要作用。早期接触邻苯二甲酸二（2-乙基己基）酯（DEHP）与成年后患精神疾病的风险增加有关。本研究旨在探索新生儿暴露于DEHP对成人PVN CRH神经元活动的影响。从PND 16至PND 22，对雄性幼鼠给予DEHP或溶剂。采用焦虑样行为、血清皮质酮和睾酮、免疫组织化学、免疫印迹、荧光原位杂交和急性活体切片电生理记录等方法，评价DEHP对成年PVN分泌CRH神经元的影响。暴露于DEHP的新生大鼠在成年后表现出增强的焦虑样行为，CORT增加。分泌型CRH神经元表现出较高的自发放电活动，但可被GABAAR阻断剂抑制。CRH神经元显示较少的放电峰，延长第一峰潜伏期，GABA逆转电位的去极化移位和增强的GABA能输入，如sIPSC的频率和振幅增加所示。GABA能传递增强伴随着GAD 67表达上调和GABABR 1、KCC 2和GAT 1表达下调。这些发现表明，新生儿暴露于DEHP永久性改变了PVN中分泌CRH神经元的特征，这可能有助于以后生活中精神疾病的发展。
Corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) play a critical role in the modulation of the hypothalamic–pituitary–adrenal (HPA) axis. Early-life exposure to di-(2-ethylhexyl) phthalate (DEHP) has been associated with an increased risk of developing psychiatric disorders in adulthood. The present work was designed to explore the impact of neonatal exposure to DEHP on adult PVN CRH neuronal activity. DEHP or vehicle was given to male rat pups from PND16 to PND22. Then, anxiety-like behaviors, serum corticosterone and testosterone, immunohistochemistry, western blotting, fluorescencein situhybridization and acuteex vivoslice electrophysiological recordings were used to evaluate the influence of DEHP on adult PVN secretory CRH neurons. Neonatal DEHP-exposed rats exhibited enhanced anxiety-like behaviors in adults, with an increase in CORT. Secretory CRH neurons showed higher spontaneous firing activity but could be inhibited by GABAAR blockers. CRH neurons displayed fewer firing spikes, prolonged first-spike latency, depolarizing shifts in GABA reversal potential and strengthened GABAergic inputs, as indicated by increases in the frequency and amplitude of sIPSCs. Enhancement of GABAergic transmission was accompanied by upregulated expression of GAD67 and downregulated expression of GABABR1, KCC2 and GAT1. These findings suggest that neonatal exposure to DEHP permanently altered the characteristics of secretory CRH neurons in the PVN, which may contribute to the development of psychiatric disorders later in life.