Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human Huntington disease gene

摘要: Loss of neurotransmitter receptors, especially glutamate and dopamine is one the pathologic hallmarks brains patients with Huntington disease (HD). Transgenic mice that express exon 1 an abnormal human HD gene (line R6/2) develop neurologic symptoms at 9–11 weeks age through unknown mechanism. Analysis receptors (GluRs) in symptomatic 12-week-old R6/2 revealed decreases compared age-matched littermate controls type metabotropic GluR (mGluR1), mGluR2, mGluR3, but not mGluR5 subtype G protein-linked mGluR, as determined by [3H]glutamate receptor binding, protein immunoblotting, situ hybridization. Ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid kainate were also decreased, while N-methyl-d-aspartic different controls. Other known to be affected decreased mice, including muscarinic cholinergic, γ-aminobutyric receptors. D1-like D2-like binding was drastically reduced one-third control 8- mice. In hybridization indicated mGluR D1 mRNA altered early 4 age, long prior onset clinical symptoms. Thus, expression precedes may contribute subsequent pathology.