Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy.
Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy.
复制标题
α1B 肾上腺素能受体的过度表达会导致细胞凋亡性神经变性：多系统萎缩。
DOI：
10.1038/82207
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Perez,DM
中科院分区：
文献类型：
--
作者：
Zuscik,MJ;Sands,S;Ross,SA;Waugh,DJ;Gaivin,RJ;Morilak,D;Perez,DM
Progress toward elucidating the function of α 1B-adrenergic receptors (α 1B ARs) in the central nervous system has been constrained by a lack of agonists and antagonists with adequate α 1B-specificity. We have obviated this constraint by generating transgenic mice engineered to overexpress either wild-type or constitutively active α 1B ARs in tissues that normally express the receptor, including the brain. All transgenic lines showed granulovacular neurodegeneration, beginning in α 1B-expressing domains of the brain and progressing with age to encompass all areas. The degeneration was apoptotic and did not occur in non-transgenic mice. Correspondingly, transgenic mice showed an age-progressive hindlimb disorder that was parkinsonian-like, as demonstrated by rescue of the dysfunction by 3, 4-dihydroxyphenylalanine and considerable dopaminergic-neuronal degeneration in the substantia nigra. Transgenic mice also had a grand mal seizure disorder accompanied by a corresponding dysplasia and neurodegeneration of the cerebral cortex. Both behavioral phenotypes (locomotor impairment and seizure) could be partially rescued with the α 1 AR antagonist terazosin, indicating that α 1 AR signaling participated directly in the pathology. Our results indicate that overstimulation of α 1B AR leads to apoptotic neurodegeneration with a corresponding multiple system atrophy indicative of Shy-Drager syndrome, a disease whose etiology is unknown.
