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Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice.
J Neurochem. 2004 Jun; 89(5):1126-36.JN

Abstract

The growing body of evidence suggests that intermediate products of alpha-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, beta-synuclein and gamma-synuclein, in neurodegeneration is less understood. We studied the effect of inactivation of gamma-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 gamma-synuclein null mutant mice. Similar reductions were revealed in alpha-synuclein and double alpha-synuclein/gamma-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.

Authors+Show Affiliations

Department of Preclinical Veterinary Sciences, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15147505

Citation

Robertson, Darren C., et al. "Developmental Loss and Resistance to MPTP Toxicity of Dopaminergic Neurones in Substantia Nigra Pars Compacta of Gamma-synuclein, Alpha-synuclein and Double Alpha/gamma-synuclein Null Mutant Mice." Journal of Neurochemistry, vol. 89, no. 5, 2004, pp. 1126-36.
Robertson DC, Schmidt O, Ninkina N, et al. Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice. J Neurochem. 2004;89(5):1126-36.
Robertson, D. C., Schmidt, O., Ninkina, N., Jones, P. A., Sharkey, J., & Buchman, V. L. (2004). Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice. Journal of Neurochemistry, 89(5), 1126-36.
Robertson DC, et al. Developmental Loss and Resistance to MPTP Toxicity of Dopaminergic Neurones in Substantia Nigra Pars Compacta of Gamma-synuclein, Alpha-synuclein and Double Alpha/gamma-synuclein Null Mutant Mice. J Neurochem. 2004;89(5):1126-36. PubMed PMID: 15147505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha/gamma-synuclein null mutant mice. AU - Robertson,Darren C, AU - Schmidt,Oliver, AU - Ninkina,Natalia, AU - Jones,Paul A, AU - Sharkey,John, AU - Buchman,Vladimir L, PY - 2004/5/19/pubmed PY - 2004/6/24/medline PY - 2004/5/19/entrez SP - 1126 EP - 36 JF - Journal of neurochemistry JO - J Neurochem VL - 89 IS - 5 N2 - The growing body of evidence suggests that intermediate products of alpha-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, beta-synuclein and gamma-synuclein, in neurodegeneration is less understood. We studied the effect of inactivation of gamma-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 gamma-synuclein null mutant mice. Similar reductions were revealed in alpha-synuclein and double alpha-synuclein/gamma-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. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15147505/Developmental_loss_and_resistance_to_MPTP_toxicity_of_dopaminergic_neurones_in_substantia_nigra_pars_compacta_of_gamma_synuclein_alpha_synuclein_and_double_alpha/gamma_synuclein_null_mutant_mice_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2004&volume=89&issue=5&spage=1126 DB - PRIME DP - Unbound Medicine ER -