Increased abundance of GABA, receptor subunit mRNAs in the brain of Long-Evans Cinnamon rats, an animal model of Wilson's disease

The abundance of mRNAs encoding various subunits of the gamma-aminobutyric acid type A (GABA(A)) receptor was examined in different regions of the bra in of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease ( WD). The measurements were performed at two different stages of disease: at 9 weeks of age, when no symptoms are evident, and at 15 weeks of age, when 90% of the animals develop jaundice. The amounts of the gamma 2L and gamma 2S subunit mRNAs in the striatum, cerebellum, and cerebral cortex of LEC r ats at 9 weeks of age were increased (+25 to +35%) compared with those in L E rats of the same age; these differences were no longer apparent in 15-wee k old animals. The amount of alpha 1 subunit mRNA was also significantly in creased (+ 30%) in the cerebellum of LEC rats at 9 weeks of age; although a smaller increase (+20%) was still evident at 15 weeks of age, this was not statistically significant. The amount of beta 2 subunit mRNA was increased in the cerebellum (+32%) and hippocampus (+21%) of LEC rats at 9 weeks of age, but no differences with LE rats were apparent at 15 weeks. The onset o f isoniazid-induced seizures in LEC rats at 9 weeks of age was significantl y delayed compared with that in LE rats. These results demonstrate abnormal expression of GABA(A) receptor subunit genes in the brain of LEC rats, and they suggest that this altered expression is associated with an increase i n GABAergic tone. (C) 1999 Elsevier Science B.V. All rights reserved.