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Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2004 Oct 12; Vol. 101 (41), pp. 14966-71. Date of Electronic Publication: 2004 Oct 01. - 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 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.
- Subjects :
- Animals
Base Sequence
Biological Transport
DNA Primers
Dopamine metabolism
Electrophysiology
Mice
Mice, Knockout
Nerve Tissue Proteins deficiency
Nerve Tissue Proteins genetics
Neurons cytology
Neurons ultrastructure
Synaptic Vesicles physiology
Synaptic Vesicles ultrastructure
Synucleins
alpha-Synuclein
beta-Synuclein
Corpus Striatum physiology
Hippocampus physiology
Nerve Tissue Proteins physiology
Neurons physiology
Synapses physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 101
- Issue :
- 41
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 15465911
- Full Text :
- https://doi.org/10.1073/pnas.0406283101