期刊
NEUROBIOLOGY OF DISEASE
卷 20, 期 1, 页码 64-73出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2005.02.001
关键词
adeno-associated virus; alpha-synuclein; neurodegeneration; neurofibrillary tangles; substantia nigra; tau
资金
- NINDS NIH HHS [R01 NS048450-01A2, R01 NS048450] Funding Source: Medline
Using a viral vector for mutant (P301L) tau, we studied the effects of gene transfer to the rat substantia nigra in terms of structural and functional properties of dopaminergic neurons. The mutant tau vector caused progressive loss of pars compacta dopaminergic neurons over time, reduced striatal dopamine content, and amphetamine-stimulated rotational behavior consistent with a specific lesion effect. In addition, structural studies demonstrated neurofibrillary tangles and neuritic pathology. Wild-type tau had similar effects on neuronal loss and rotational behavior. In contrast, mutant alpha-synuclein vectors did not induce rotational behavior, although alpha-synuclein filaments formed in nigrostriatal axons. Dopamine neuron function is affected by tau gene transfer and appears to be more susceptible to tau- rather than alpha-synuclein-related damage in this model. Both tau and a-synuclein are important for substantia nigra neurodegeneration models in rats, further indicating their potential as therapeutic targets for human diseases involving loss of dopamine neurons. (c) 2005 Elsevier Inc. All rights reserved.
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