期刊
NEUROBIOLOGY OF DISEASE
卷 26, 期 2, 页码 312-322出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2006.12.021
关键词
Parkinson's disease; parkin; alpha-synuclein; MPTP; DSP-4; substantia nigra; locus coeruleus; dopamine; norepinephrine
资金
- NINDS NIH HHS [P50 NS038377, NS48206, NS38377, R01 NS048206] Funding Source: Medline
Mutations in the parkin gene cause autosomal recessive familial Parkinson's disease (PD). Parkin-deficient mouse models fail to recapitulate nigrostriatal dopaminergic neurodegeneration as seen in PD, but produce deficits in dopaminergic neurotransmission and noradrenergic-dependent behavior. Since sporadic PD is thought to be caused by a combination of genetic susceptibilities and environmental factors, we hypothesized that neurotoxic insults from catecholaminergic toxins would render parkin knockout mice more vulnerable to neurodegeneration. Accordingly, we investigated the susceptibility of catecholaminergic neurons in parkin knockout mice to the potent dopaminergic and noradrenergic neurotoxins 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) and N-(2-chloroethyl)-N-ethyl2-bromobenzylamine (DSP-4) respectively. We report that nigrostriatal dopaminergic neurons in parkin knockout mice do not show increased susceptibility to the parkinsonian neurotoxin, MPTP, in acute, subacute and chronic dose regimens of the neurotoxin. Additionally, parkin knockout mice do not show increased vulnerability to the noradrenergic neurotoxin, DSP-4, regarding levels of norepinephrine in cortex, brain stem and spinal cord. These findings suggest that absence of parkin in mice does not increase susceptibility to the loss of catecholaminergic neurons upon exposure to both dopaminergic and noradrenergic neurotoxins. (c) 2007 Elsevier Inc. All rights reserved.
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