Striatal dopamine transmission is subtly modified in human A53T(Alpha)-synuclein overexpressing mice.

Journal article

Mutations in, or elevated dosage of, SNCA, the gene for (Alpha)-synuclein ((Alpha)-syn), cause familial Parkinson's disease (PD). Mouse lines overexpressing the mutant human A53T(Alpha)-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of (Alpha)-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA) signalling. In addition A53T(Alpha)-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53T(Alpha)-syn, and explored whether A53T(Alpha)-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53T(Alpha)-syn-overexpressing mice, at up to 24 months. In A53T(Alpha)-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53T(Alpha)-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs) were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53T(Alpha)-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53T(Alpha)-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction.

Authors: Platt, N; Gispert, S; Auburger, G; Cragg, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PloS one
• Volume: 7
• Issue: 5
• Pages: e36397
• Publication date: 2012-01-01
• DOI: 10.1371/journal.pone.0036397
• EISSN: 1932-6203
• ISSN: 1932-6203
• Language: English
• Keywords: Mice, Transgenic; Mutation; Amino Acid Substitution; Gene Expression; Dopamine; Synaptic Transmission; Mice; Female; Corpus Striatum; Animals; alpha-Synuclein; Humans