期刊
NEUROBIOLOGY OF DISEASE
卷 27, 期 2, 页码 141-150出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2007.03.014
关键词
DJ-1; Parkinson; dopamine transporter; striatum; MPTP; substantia nigra; transgenic; dopamine
资金
- Intramural NIH HHS Funding Source: Medline
- NIEHS NIH HHS [ES 012077, ES 01268] Funding Source: Medline
Mutations in the gene for DJ-1 have been associated with early-onset autosomal recessive parkinsonism. Previous studies of null DJ-1 mice have shown alterations in striatal dopamine (DA) transmission with no DAergic cell loss. Here we characterize a new line of DJ-1-deficient mice. A subtle locomotor deficit was present in the absence of a change in striatal DA levels. However, increased [H-3]-DA synaptosomal uptake and [I-125]-RTI-121 binding were measured in null DJ-1 vs. wild-type mice. Western analyses of synaptosomes revealed significantly higher dopamine transporter (DAT) levels in pre-synaptic membrane fractions. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure exacerbated striatal DA depletion in null DJ-1 mice with no difference in DAergic nigral cell loss. Furthermore, increased 1-methyl-4-phenylpyridinium (MPP+) synaptosomal uptake and enhanced MPP+ accumulation were measured in DJ-1-deficient vs. control striatum. Thus, under null DJ-1 conditions, DAT changes likely contribute to altered DA neurotransmission and enhanced sensitivity to toxins that utilize DAT for nigrostriatal entry. (c) 2007 Published by Elsevier Inc.
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