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Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of γ-synuclein, α-synuclein and double α/γ- synuclein null mutant mice

Robertson, Darren C., Schmidt, Oliver, Ninkina, Natalia, Jones, Paul A., Sharkey, John and Buchman, Vladimir 2004. Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of γ-synuclein, α-synuclein and double α/γ- synuclein null mutant mice. Journal of Neurochemistry 89 (5) , pp. 1126-1136. 10.1111/j.1471-4159.2004.02378.x

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Abstract

The growing body of evidence suggests that intermediate products of -synuclein aggregation cause death of sensitive populations of neurones, particularly dopaminergic neurones, which is a critical event in the development of Parkinson's disease and other synucleinopathies. The role of two other members of the family, ?-synuclein and -synuclein, in neurodegeneration is less understood. We studied the effect of inactivation of -synuclein gene on mouse midbrain dopaminergic neurones. Reduced number of dopaminergic neurones was found in substantia nigra pars compacta (SNpc) but not in ventral tegmental area (VTA) of early post-natal and adult -synuclein null mutant mice. Similar reductions were revealed in -synuclein and double -synuclein/-synuclein null mutant animals. However, in none of these mutants did this lead to significant changes of striatal dopamine or dopamine metabolite levels and motor dysfunction. In all three studied types of null mutants, dopaminergic neurones of SNpc were resistant to methyl-phenyl-tetrahydropyridine (MPTP) toxicity. We propose that both synucleins are important for effective survival of SNpc neurones during critical period of development but, in the absence of these proteins, permanent activation of compensatory mechanisms allow many neurones to survive and become resistant to certain toxic insults.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: Development ; Knockout mice ; MPTP ; Substantia nigra ; Synuclein
ISSN: 0022-3042
Last Modified: 04 Jun 2017 01:37
URI: http://orca.cf.ac.uk/id/eprint/1002

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