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[新生儿反复惊厥对大鼠脑内γ-氨基丁酸A受体α1和β2亚基表达的短期影响]

[Short-term effects of recurrent neonatal seizures on gamma-aminobutyric acid A receptor alpha1 and beta2 subunit expression in the rat brain].

作者信息

Bo Tao, Wang Tuan-Mei, Zhu Xiao-Hua, Li Jian, Li Xing-Fang, Chen Yong, Mao Ding-An

机构信息

Department of Pediatr-ics, Second Xiangya Hospital, Central South University, Changsha 410011, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2008 Jun;10(3):371-5.

PMID:18554471
Abstract

OBJECTIVE

To investigate the short-term effects of flurothyl-induced neonatal recurrent seizures on gamma-aminobutyric acid A receptor (GABAAR) alpha1 and beta2 subunit expression in the rat brain, and to study the relationship between the alterations of GABAAR subunits in the developing brain and seizure-induced brain injury.

METHODS

Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into two groups: control and seizure. Seizures were induced by inhalant flurothyl daily for six consecutive days. The expression of GABAAR alpha1 and beta2 subunits protein in the cerebral cortex and the hippocampus were detected by Western blot and immunohistochemistry method 1 and 7 days after recurrent seizures.

RESULTS

Compared to the control, the accumulated optical density (AOD) of GABAAR alpha1 subunit immunoreactivity (IR) in the parietal cortex, the CA3-CA4 regions and the dentate gyrus in seizure rats increased significantly 1 day after recurrent seizures (P<0.05). The AOD of GABAAR alpha1 subunit IR in the parietal cortex, the CA1-CA4 regions and the dentate gyrus in seizure rats increased significantly 7 days after recurrent seizures compared with the control (P<0.05). The expression of GABAAR alpha1 subunit in the hippicampus and the cerebral cortex increased significantly in seizure rats compared with that in control rats 1 and 7 days after recurrent seizures. After 7 days of recurrent seizures, the AOD of GABAAR beta2 subunit IR in the CA1-CA2 regions increased significantly in the seizure group compared with that in the control group (P<0.05), but the AOD of GABAAR beta2 subunit IR in the thalamus decreased significantly in the seizure group compared with that in the control group (P<0.05). The expression of GABAAR beta2 subunit protein in the hippocampus increased significantly in the seizure group compared with that in the control group 7 days after recurrent seizures (P<0.05).

CONCLUSIONS

Recurrent neonatal seizures may result in the short-term alterations of GABAAR alpha1 and beta2 subunits expression in the cerebral cortex and the hippocampus in rats, suggesting the alterations of GABAAR subunit expression may be related to the developing brain injury following recurrent seizures.

摘要

目的

探讨氟替尔诱导新生大鼠反复惊厥对大鼠脑内γ-氨基丁酸A受体(GABAAR)α1和β2亚基表达的短期影响,并研究发育中脑内GABAAR亚基改变与惊厥性脑损伤之间的关系。

方法

将64只7日龄的Sprague-Dawley大鼠随机分为两组:对照组和惊厥组。连续6天每日通过吸入氟替尔诱导惊厥。在反复惊厥后1天和7天,采用蛋白质免疫印迹法和免疫组织化学方法检测大脑皮质和海马中GABAARα1和β2亚基蛋白的表达。

结果

与对照组相比,反复惊厥后1天,惊厥组大鼠顶叶皮质、CA3-CA4区和齿状回中GABAARα1亚基免疫反应性(IR)的累积光密度(AOD)显著增加(P<0.05)。反复惊厥后7天,惊厥组大鼠顶叶皮质、CA1-CA4区和齿状回中GABAARα1亚基IR的AOD与对照组相比显著增加(P<0.05)。反复惊厥后1天和7天,惊厥组大鼠海马和大脑皮质中GABAARα1亚基的表达与对照组相比显著增加。反复惊厥7天后,惊厥组CA1-CA2区GABAARβ2亚基IR的AOD与对照组相比显著增加(P<0.05),但惊厥组丘脑GABAARβ2亚基IR的AOD与对照组相比显著降低(P<0.05)。反复惊厥7天后,惊厥组大鼠海马中GABAARβ2亚基蛋白的表达与对照组相比显著增加(P<0.05)。

结论

新生大鼠反复惊厥可能导致大鼠大脑皮质和海马中GABAARα1和β2亚基表达的短期改变,提示GABAAR亚基表达的改变可能与反复惊厥后发育中的脑损伤有关。

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