Brain neurotransmitter deficits in mice transgenic for the Huntington's disease mutation

被引:75
|
作者
Reynolds, GP [1 ]
Dalton, CF
Tillery, CL
Mangiarini, L
Davies, SW
Bates, GP
机构
[1] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England
[2] Guys Hosp, GKT Med & Dent Sch, Div Med & Mol Genet, London, England
[3] UCL, Dept Anat & Dev Biol, London, England
基金
英国惠康基金;
关键词
Huntington's disease; transgenic mice; catecholamines; 5-hydroxytryptamine; GABA; neurodegeneration;
D O I
10.1046/j.1471-4159.1999.721773.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Huntington's disease (HD) is associated with an expansion in the CAG repeat sequence of a gene on chromosome 4, resulting in a neurodegenerative process particularly affecting the striatum and with profound but selective changes in content of various neurotransmitters. Recently, transgenic mice expressing a fragment of the human HD gene containing a large CAG expansion have been generated; these mice exhibit a progressive neurological phenotype that includes motor disturbances, as well as neuronal deficits. To investigate their underlying neurotransmitter pathology, we have determined concentrations of GABA, glutamate, and the monoamine neurotransmitters in several brain regions in these mice and control animals at times before and after the emergence of the behavioural phenotype. in contrast to the findings in HD, striatal GABA was unaffected, although a deficit was observed in the cerebellum, consistent with a dysfunction of Purkinje cells. Losses of the monoamine transmitters were observed, some of which are not seen in HD. Thus, 5-hydroxytryptamine and, to a greater extent, 5-hydroxyindoleacetic acid levels were diminished in all brain regions studied, and noradrenaline was particularly affected in the hippocampus. Dopamine was decreased in the striatum in older animals, parallelling evidence for diminished dopaminergic activity in HD.
引用
收藏
页码:1773 / 1776
页数:4
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