PMID:18333965

Citation	Senior, SL, Ninkina, N, Deacon, R, Bannerman, D, Buchman, VL, Cragg, SJ and Wade-Martins, R (2008) Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein. Eur. J. Neurosci. 27:947-57
Abstract	Alpha-synuclein is intimately involved in the pathogenesis of Parkinson's disease, and has been implicated in the regulation of synthesis, release and reuptake of dopamine (DA). However, mice lacking members of the synuclein family have been reported to display no overt behavioural phenotype. This may be a result of compensatory upregulation of other synucleins during development. Here we report on behaviour and DA synapse function of alpha-synuclein null, gamma-synuclein null, and alpha-gamma-synuclein double-null knockout mice. Double-null mice were hyperactive in a novel environment and alternated at a lower rate in a T-maze spontaneous alternation task, a phenotype reminiscent of mice expressing reduced levels of the DA transporter. To investigate a possible hyperdopaminergic phenotype in alpha-gamma-synuclein double-null mice, we used fast-scan cyclic voltammetry at carbon-fibre microelectrodes to assess DA release and reuptake in striatal slices from wild-type, alpha-null, gamma-null and double-null mice in real time. Double-null mice were found to have a twofold increase in the extracellular concentration of DA detected after discrete electrical stimuli in the striatum. By measuring the rate of reuptake of DA and tissue DA content in these animals, we showed that the observed increase in size of striatal DA transients was not attributable to a decrease in reuptake of DA via the DA transporter, and can not be attributed to an increase in tissue DA levels in the striatum. Rather, we propose that loss of both alpha- and gamma-synuclein causes an increase in release probability from dopaminergic synapses.
Links	PubMed PMC3145106 Online version:10.1111/j.1460-9568.2008.06055.x
Keywords	Animals; Behavior, Animal/physiology; Chromatography, High Pressure Liquid; Corpus Striatum/metabolism; Dopamine/secretion; Extracellular Fluid/chemistry; Female; Glucose/metabolism; Hyperkinesis/physiopathology; Maze Learning; Mice; Mice, Knockout; Microelectrodes; Motor Activity/physiology; Organ Culture Techniques; Protein Isoforms/deficiency; Synapses/metabolism; alpha-Synuclein/deficiency; alpha-Synuclein/genetics; gamma-Synuclein/deficiency; gamma-Synuclein/genetics
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.