Department of Physiology, School of Medicine, University of Occupational and Environmental Health, and Kokura Rehabilitation Hospital, Yahatanishi-ku, Kitakyushu, Japan.
Stress. 2012 Jul;15(4):435-42. doi: 10.3109/10253890.2011.637185. Epub 2011 Dec 5.
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.
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。
