Expression of GABAA receptor subunits in the hippocampus of the rat after kainic acid-induced seizures

被引:67
|
作者
Sperk, G [1 ]
Schwarzer, C [1 ]
Tsunashima, K [1 ]
Kandlhofer, S [1 ]
机构
[1] Univ Innsbruck, Dept Pharmacol, A-6020 Innsbruck, Austria
关键词
benzodiazepines; dentate gyrus; limbic system; mossy fibers; receptor adaptation; temporal lobe epilepsy;
D O I
10.1016/S0920-1211(98)00046-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The GABA(A) receptor is a ligand gated chloride channel consisting of five membrane spanning proteins for which 13 different genes have been identified in the mammalian brain. The present review summarizes recent work from our laboratory on the characterization of the immunocytochemical distribution of these GABA(A) receptor subunits in the rat brain and changes in immunoreactivity and mRNA expression after kainic acid-induced status epilepticus. A heterogeneous distribution of immunoreactive GABA(A) receptor subunits was observed. The most abundant ones were: alpha(1), alpha(2), alpha(4), alpha(5), beta(2), beta(3), gamma(2), delta. alpha(1), beta(2), and gamma(2) were about equally distributed in all subfields of the hippocampus; alpha(4)- and delta-subunits were preferentially found in the dentate molecular layer and in CA1; alpha(2) was localized to the dentate molecular layer and CA3; alpha(5) was found in the dendritic areas of CA1 to CA3; and beta(1) was preferentially seen in CA2. alpha(1), beta(2), gamma(2) and delta were highly concentrated in interneurons. Kainic acid-induced seizures caused acute and chronic changes in the expression of mRNAs and immunoreactive proteins. Acute changes included decreases in alpha(2), alpha(5), beta(1), beta(3), gamma(2) and delta mRNA levels (by about 25-50%), accompanied by increases (by about 50%) in alpha(1), alpha(4), and beta(2) messages in granule cells (after 6-12 h). Chronic changes, characterized by losses in mRNA and immunoreactive proteins in CA1 and CA3, are undoubtedly due to seizure-related cell damage. However, compensatory expression of alpha(2) and beta(3) subunits, especially in CA3b/c, was observed. Furthermore, increases in mRNAs and immunoreactive proteins were seen for alpha(1), alpha(2), alpha(4), beta(1), beta(2), beta(3) and gamma(2) in granule cells and in the molecular layer of the dentate gyrus at 7-30 days after kainic acid injection. The changes in the expression of GABA(A) receptor subunits, observed in practically all hippocampal subfields, may reflect altered GABA-ergic transmission during development of the epileptic syndrome. Increased expression of GABA(A) receptor subunits in the dendritic field of granule cells and CA3 suggest that GABA-ergic inhibition may be augmented at these levels. However, the lasting preservation of alpha(1)-, beta(2)-, and gamma(2)-subunits in interneurons could provide a basis for augmented inhibition of GABA-ergic interneurons, leading to net disinhibition. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:129 / 139
页数:11
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