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Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates.
Neurobiol Dis. 2005 Dec; 20(3):898-906.ND

Abstract

Changes in the expression of alpha-synuclein are likely to underlie its normal function as well as its role in pathological processes. The relationship between toxic injury and alpha-synuclein expression was assessed in the substantia nigra of squirrel monkeys treated with a single injection of MPTP and sacrificed 1 week or 1 month later. At 1 week, when stereological cell counting revealed only a small decrease (-10%) in the number of dopaminergic neurons, alpha-synuclein mRNA and protein were markedly enhanced. Increased alpha-synuclein immunoreactivity was evident at the level of neuronal fibers whereas nigral cell bodies were devoid of detectable protein. At 1 month post-MPTP, neuronal loss rose to 40%. Both alpha-synuclein mRNA and protein remained elevated but, noticeably, a robust alpha-synuclein immunoreactivity characterized a significant number of cell bodies. Neuromelanin granules are hallmarks of dopaminergic neurons in primates. Therefore, the number of alpha-synuclein-positive cells that also contained neuromelanin was counted throughout the substantia nigra. At 1 month, the vast majority of alpha-synuclein-immunoreactive neurons contained neuromelanin, and approximately 80% of the dopaminergic cell bodies that survived MPTP toxicity stained positive for alpha-synuclein. The results indicate that a single toxic insult is capable of inducing a sustained alpha-synuclein up-regulation in the primate brain. They support a direct relationship between neuronal injury and enhanced alpha-synuclein expression, and suggest that protein elevation within cell bodies may be a late feature of neurons that have endured a toxic stress.

Authors+Show Affiliations

The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, California 94089, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16006134

Citation

Purisai, Maya G., et al. "Alpha-synuclein Expression in the Substantia Nigra of MPTP-lesioned Non-human Primates." Neurobiology of Disease, vol. 20, no. 3, 2005, pp. 898-906.
Purisai MG, McCormack AL, Langston WJ, et al. Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates. Neurobiol Dis. 2005;20(3):898-906.
Purisai, M. G., McCormack, A. L., Langston, W. J., Johnston, L. C., & Di Monte, D. A. (2005). Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates. Neurobiology of Disease, 20(3), 898-906.
Purisai MG, et al. Alpha-synuclein Expression in the Substantia Nigra of MPTP-lesioned Non-human Primates. Neurobiol Dis. 2005;20(3):898-906. PubMed PMID: 16006134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates. AU - Purisai,Maya G, AU - McCormack,Alison L, AU - Langston,William J, AU - Johnston,Louisa C, AU - Di Monte,Donato A, Y1 - 2005/07/11/ PY - 2005/03/05/received PY - 2005/05/10/revised PY - 2005/05/25/accepted PY - 2005/7/12/pubmed PY - 2006/3/10/medline PY - 2005/7/12/entrez SP - 898 EP - 906 JF - Neurobiology of disease JO - Neurobiol Dis VL - 20 IS - 3 N2 - Changes in the expression of alpha-synuclein are likely to underlie its normal function as well as its role in pathological processes. The relationship between toxic injury and alpha-synuclein expression was assessed in the substantia nigra of squirrel monkeys treated with a single injection of MPTP and sacrificed 1 week or 1 month later. At 1 week, when stereological cell counting revealed only a small decrease (-10%) in the number of dopaminergic neurons, alpha-synuclein mRNA and protein were markedly enhanced. Increased alpha-synuclein immunoreactivity was evident at the level of neuronal fibers whereas nigral cell bodies were devoid of detectable protein. At 1 month post-MPTP, neuronal loss rose to 40%. Both alpha-synuclein mRNA and protein remained elevated but, noticeably, a robust alpha-synuclein immunoreactivity characterized a significant number of cell bodies. Neuromelanin granules are hallmarks of dopaminergic neurons in primates. Therefore, the number of alpha-synuclein-positive cells that also contained neuromelanin was counted throughout the substantia nigra. At 1 month, the vast majority of alpha-synuclein-immunoreactive neurons contained neuromelanin, and approximately 80% of the dopaminergic cell bodies that survived MPTP toxicity stained positive for alpha-synuclein. The results indicate that a single toxic insult is capable of inducing a sustained alpha-synuclein up-regulation in the primate brain. They support a direct relationship between neuronal injury and enhanced alpha-synuclein expression, and suggest that protein elevation within cell bodies may be a late feature of neurons that have endured a toxic stress. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/16006134/Alpha_synuclein_expression_in_the_substantia_nigra_of_MPTP_lesioned_non_human_primates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(05)00160-9 DB - PRIME DP - Unbound Medicine ER -