文章基本信息

标题：Double-knockout mice for α- and β-synucleins: Effect on synaptic functions
本地全文：下载
作者：Sreeganga Chandra ; Francesco Fornai ; Hyung-Bae Kwon 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：41
页码：14966-14971
DOI：10.1073/pnas.0406283101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：An abundant presynaptic protein, {alpha}-synuclein, is centrally involved in the pathogenesis of Parkinson's disease. However, conflicting data exist about the normal function of {alpha}-synuclein, possibly because {alpha}-synuclein is redundant with the very similar {beta}-synuclein. To investigate the functions of synucleins systematically, we have now generated single- and double-knockout (KO) mice that lack {alpha}- and/or {beta}-synuclein. We find that deletion of synucleins in mice does not impair basic brain functions or survival. We detected no significant changes in the ultrastructure of synuclein-deficient synapses, in short- or long-term synaptic plasticity, or in the pool size or replenishment of recycling synaptic vesicles. However, protein quantitations revealed that KO of synucleins caused selective changes in two small synaptic signaling proteins, complexins and 14-3-3 proteins. Moreover, we found that dopamine levels in the brains of double-KO but not single-KO mice were decreased by {approx}20%. In contrast, serotonin levels were unchanged, and dopamine uptake and release from isolated nerve terminals were normal. These results show that synucleins are not essential components of the basic machinery for neurotransmitter release but may contribute to the long-term regulation and/or maintenance of presynaptic function.