Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn), cause familial Parkinson's disease (PD). Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and de...

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Autores principales:	Nicola J Platt, Suzana Gispert, Georg Auburger, Stephanie J Cragg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70e3bba895d94bb0ae050cdb506c4310
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spelling	oai:doaj.org-article:70e3bba895d94bb0ae050cdb506c43102021-11-18T07:19:48ZStriatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.1932-620310.1371/journal.pone.0036397https://doaj.org/article/70e3bba895d94bb0ae050cdb506c43102012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22570709/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn), cause familial Parkinson's disease (PD). Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-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 A53Tα-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 A53Tα-syn, and explored whether A53Tα-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 A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-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 A53Tα-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, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-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.Nicola J PlattSuzana GispertGeorg AuburgerStephanie J CraggPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36397 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicola J Platt Suzana Gispert Georg Auburger Stephanie J Cragg Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.
description	Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn), cause familial Parkinson's disease (PD). Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-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 A53Tα-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 A53Tα-syn, and explored whether A53Tα-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 A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-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 A53Tα-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, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-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.
format	article
author	Nicola J Platt Suzana Gispert Georg Auburger Stephanie J Cragg
author_facet	Nicola J Platt Suzana Gispert Georg Auburger Stephanie J Cragg
author_sort	Nicola J Platt
title	Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.
title_short	Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.
title_full	Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.
title_fullStr	Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.
title_full_unstemmed	Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.
title_sort	striatal dopamine transmission is subtly modified in human a53tα-synuclein overexpressing mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/70e3bba895d94bb0ae050cdb506c4310
work_keys_str_mv	AT nicolajplatt striataldopaminetransmissionissubtlymodifiedinhumana53tasynucleinoverexpressingmice AT suzanagispert striataldopaminetransmissionissubtlymodifiedinhumana53tasynucleinoverexpressingmice AT georgauburger striataldopaminetransmissionissubtlymodifiedinhumana53tasynucleinoverexpressingmice AT stephaniejcragg striataldopaminetransmissionissubtlymodifiedinhumana53tasynucleinoverexpressingmice
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Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

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