期刊
NEUROBIOLOGY OF DISEASE
卷 65, 期 -, 页码 112-123出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2014.01.017
关键词
Dopamine-deficient mice; Neurodegeneration; Tyrosine hydroxylase; Viral inactivation; 6-Hydroxydopamine; Executive function
资金
- Pacific Northwest Udall Center [P50-NS062684]
Although the cardinal features of Parkinson's disease (PD) are motor symptoms, PD also causes cognitive deficits including cognitive flexibility and working memory, which are strongly associated with prefrontal cortex (PFC) functions. Yet, early stage PD is not characterized by pathology in the PFC but by a loss of dopaminergic (DA) projections from the substantia nigra to the dorsal striatum. Moreover, the degree to which PD symptoms can be ascribed to the loss of DA alone or to the loss of DA neurons is unknown. We addressed these issues by comparing mouse models of either chronic DA depletion or loss of DA projections to the dorsal striatum. We achieved equal levels of striatal DA reduction in both models which ranged from mild (similar to 25%) to moderate (similar to 60%). Both models displayed DA concentration-dependent reductions of motor function as well as mild deficits of cognitive flexibility and working memory. Interestingly, whereas both motor function and cognitive flexibility were more severely impaired after mild ablation of DA neurons as compared to mild loss of DA alone, both models had equal deficits after moderate loss of DA. Our results confirm contributions of nigro-striatal dopamine signaling to cognitive behaviors that are affected in early stage PD. Furthermore, our findings suggest that the phenotype after ablation of DA neurons accrues from factors beyond the mere loss of DA. Published by Elsevier Inc.
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