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诱导大鼠海人酸诱导的癫痫发作后蓝斑中精氨酸加压素增强型绿色荧光蛋白的表达。

Induction of arginine vasopressin-enhanced green fluorescent protein expression in the locus coeruleus following kainic acid-induced seizures in rats.

机构信息

Department of Physiology, School of Medicine, University of Occupational and Environmental Health, and Kokura Rehabilitation Hospital, Yahatanishi-ku, Kitakyushu, Japan.

出版信息

Stress. 2012 Jul;15(4):435-42. doi: 10.3109/10253890.2011.637185. Epub 2011 Dec 5.

Abstract

Seizure causes autonomic, neuroendocrine and stress responses. We examined the effects of kainic acid (KA)-induced seizures on the expression of the arginine vasopressin (AVP)-enhanced green fluorescent protein (eGFP) in the locus coeruleus (LC), an area known to contain noradrenergic cells, in AVP-eGFP transgenic male and female rats, with the rationale to identify stressors which induce AVP synthesis in the LC. Subcutaneous (s.c.) administration of KA caused a progressive development of seizure behavior within 24 h. AVP-eGFP fluorescence in the LC was detected 6, 24, and 48 h and 1 week after administration of KA (12 mg/kg). From a nearly undetectable level, it reached a maximum at 48 h after s.c. administration of KA and returned to the basal levels after 2 weeks. AVP-eGFP fluorescence in the LC after s.c. administration of KA was significantly reduced by the pretreatment with MK-801 (nonselective N-methyl-D-aspartate (NMDA) receptor antagonist). In the KA-administered rats, immunohistochemistry for tyrosine hydroxylase (TH) revealed that the eGFP fluorescence was co-localized with TH-immuno-reactivity in the LC. These results suggest that the synthesis of AVP-eGFP is potentially up-regulated in noradrenergic neurons in the LC after KA-induced seizures through the activation of NMDA receptors.

摘要

癫痫发作会引起自主神经、神经内分泌和应激反应。我们研究了海人酸(KA)诱导的癫痫发作对蓝斑(LC)中精氨酸加压素(AVP)增强型绿色荧光蛋白(eGFP)表达的影响,LC 是已知含有去甲肾上腺素能细胞的区域,研究对象为 AVP-eGFP 转基因雄性和雌性大鼠,目的是确定在 LC 中诱导 AVP 合成的应激源。皮下(s.c.)给予 KA 后,在 24 小时内逐渐出现癫痫发作行为。在给予 KA(12 mg/kg)后 6、24、48 小时和 1 周检测到 LC 中 AVP-eGFP 荧光。从几乎无法检测到的水平,它在 s.c.给予 KA 后 48 小时达到最大值,在 2 周后恢复到基础水平。s.c.给予 KA 后,LC 中的 AVP-eGFP 荧光通过 MK-801(非选择性 N-甲基-D-天冬氨酸(NMDA)受体拮抗剂)预处理显著减少。在 KA 给药大鼠中,酪氨酸羟化酶(TH)免疫组织化学显示,eGFP 荧光与 LC 中的 TH 免疫反应性共定位。这些结果表明,在 KA 诱导的癫痫发作后,通过 NMDA 受体的激活,LC 中的去甲肾上腺素能神经元中 AVP-eGFP 的合成可能被上调。

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