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Absence of α-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice

Al-Wandi, Abdelmojib, Ninkina, Natalia ORCID:, Millership, Steven, Williamson, S. J. M., Jones, P. A. and Buchman, Vladimir L. ORCID: 2010. Absence of α-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice. Neurobiology of Aging 31 (5) , pp. 796-804. 10.1016/j.neurobiolaging.2008.11.001

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Despite numerous evidences for neurotoxicity of overexpressed α-synuclein, a protective function was suggested for endogenous α-synuclein and other members of the synuclein family. This protective role is most important for and evident in presynaptic terminals, where synucleins are normally accumulated. However, mice lacking synucleins display no adverse phenotype. In particular, no significant changes in striatal dopamine metabolism and only subtle deficit of dopaminergic neurons in the substantia nigra were found in juvenile or adult mice. To assess whether aging and synuclein deficiency may have additive detrimental effect on the nigrostriatal system, we studied dopaminergic neurons of the substantia nigra and their striatal synapses in 24–26-month-old α-synuclein and γ-synuclein null mutant mice. Significant ∼36% reduction of the striatal dopamine was found in aging α-synuclein, but not γ-synuclein null mutant mice when compared to age-matching wild type mice. This was accompanied by the reduction of TH-positive fibers in the striatum and decrease of striatal levels of TH and DAT. However, no progressive loss of TH-positive neurons was revealed in the substantia nigra of synuclein-deficient aging animals. Our results are consistent with a hypothesis that α-synuclein is important for normal function and integrity of synapses, and suggest that in the aging nervous system dysfunction of this protein could become a predisposition factor for the development of nigrostriatal pathology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords: Synuclein; Null mutant; Synucleinopathy; Parkinson’s disease; Ageing; Dopaminergic neurons; Substantia nigra; Neuroprotection; Synaptoprotection
Publisher: Elsevier
ISSN: 0197-4580
Last Modified: 02 Dec 2022 11:46

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