Increased abundance of GABAA 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 (GABAA) receptor was examined in different regions of the brain 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 gamma2L and gamma2S subunit mRNAs in the striatum, cerebellum, and cerebral cortex of LEC rats at 9 weeks of age were increased (+25 to +35%) compared with those in LE rats of the same age; these differences were no longer apparent in 15-week old animals. The amount of alpha1 subunit mRNA was also significantly increased (+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 beta2 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 of isoniazid-induced seizures in LEC rats at 9 weeks of age was significantly delayed compared with that in LE rats. These results demonstrate abnormal expression of GABAA receptor subunit genes in the brain of LEC rats, and they suggest that this altered expression is associated with an increase in GABAergic tone.
Follesa
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P
Department of Experimental Biology 'Bernardo Loddo,' University of Cagliari, Via Palabanda 12, 09123 Cagliari, Italy.follesa@vaxca1.unica .it
Mallei
A
A
Floris
S
S
Mostallino
M C
MC
Sanna
E
E
Biggio
G
G
D000375:Aging / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D006527:Hepatolenticular Degeneration / Q000378:metabolism*; D007538:Isoniazid / Q000633:toxicity; D010446:Peptide Fragments / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D020332:Rats, Inbred LEC; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced
D010446:Peptide Fragments; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D007538:Isoniazid