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Double-knockout mice for [alpha]- and [beta]-synucleins: effect on synaptic functions

Authors :
Chandra, Sreeganga
Fornai, Francesco
Kwon, Hyung-Bae
Yazdani, Umar
Atasoy, Deniz
Liu, Xinran
Hammer, Robert E.
Battaglia, Giuseppe
German, Dwight C.
Castillo, Pablo E.
Sudhof, Thomas C.
Source :
Proceedings of the National Academy of Sciences of the United States. Oct 12, 2004, Vol. 101 Issue 41, p14966, 6 p.
Publication Year :
2004

Abstract

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 [approximately equal to] 20%. In contrast, serotonin levels were unchanged, and dopamine uptake and release from isolated nerve terminals were normal. These results show that synudeins 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.

Details

Language :
English
ISSN :
00278424
Volume :
101
Issue :
41
Database :
Gale General OneFile
Journal :
Proceedings of the National Academy of Sciences of the United States
Publication Type :
Academic Journal
Accession number :
edsgcl.123934054