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Decreased alpha-synuclein expression in the aging mouse substantia nigra.
Exp Neurol. 2009 Dec; 220(2):359-65.EN

Abstract

Because of its normal function in synaptic plasticity and pathologic involvement in age-related neurodegenerative diseases, the protein alpha-synuclein could play an important role in aging processes. Here we compared alpha-synuclein expression in the substantia nigra and other brain regions of young (2-month-old), middle-aged (10-month-old), and old (20-month-old) mice. Levels of nigral alpha-synuclein mRNA, as assessed by both in situ hybridization and qPCR, were high in young mice and progressively declined in middle-aged and old animals. This age-dependent mRNA loss was paralleled by a marked reduction of alpha-synuclein protein; immunoreactivity of midbrain sections stained with an anti-alpha-synuclein antibody was most robust in 2-month-old mice and weakest in 20-month-old animals. Lowering of nigral alpha-synuclein could not be explained by a loss of dopaminergic neurons and was relatively specific since no change in beta-synuclein mRNA and protein occurred with advancing age. Finally, age-related decreases in alpha-synuclein were widespread throughout the mouse brain, affecting other regions (e.g., hippocampus) besides the substantia nigra. The data suggest that loss of alpha-synuclein could contribute to or be a marker of synaptic dysfunction in the aging brain. They also emphasize important differences in alpha-synuclein expression between rodents and primates since earlier reports have shown a marked elevation of alpha-synuclein protein in the substantia nigra of older humans and non-human primates.

Authors+Show Affiliations

The Parkinson's Institute, 675 Almanor Avenue, Sunnyvale, CA 94085, USA.No 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

19800328

Citation

Mak, Sally K., et al. "Decreased Alpha-synuclein Expression in the Aging Mouse Substantia Nigra." Experimental Neurology, vol. 220, no. 2, 2009, pp. 359-65.
Mak SK, McCormack AL, Langston JW, et al. Decreased alpha-synuclein expression in the aging mouse substantia nigra. Exp Neurol. 2009;220(2):359-65.
Mak, S. K., McCormack, A. L., Langston, J. W., Kordower, J. H., & Di Monte, D. A. (2009). Decreased alpha-synuclein expression in the aging mouse substantia nigra. Experimental Neurology, 220(2), 359-65. https://doi.org/10.1016/j.expneurol.2009.09.021
Mak SK, et al. Decreased Alpha-synuclein Expression in the Aging Mouse Substantia Nigra. Exp Neurol. 2009;220(2):359-65. PubMed PMID: 19800328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decreased alpha-synuclein expression in the aging mouse substantia nigra. AU - Mak,Sally K, AU - McCormack,Alison L, AU - Langston,J William, AU - Kordower,Jeffrey H, AU - Di Monte,Donato A, Y1 - 2009/10/01/ PY - 2009/07/23/received PY - 2009/09/09/revised PY - 2009/09/24/accepted PY - 2009/10/6/entrez PY - 2009/10/6/pubmed PY - 2009/12/16/medline SP - 359 EP - 65 JF - Experimental neurology JO - Exp Neurol VL - 220 IS - 2 N2 - Because of its normal function in synaptic plasticity and pathologic involvement in age-related neurodegenerative diseases, the protein alpha-synuclein could play an important role in aging processes. Here we compared alpha-synuclein expression in the substantia nigra and other brain regions of young (2-month-old), middle-aged (10-month-old), and old (20-month-old) mice. Levels of nigral alpha-synuclein mRNA, as assessed by both in situ hybridization and qPCR, were high in young mice and progressively declined in middle-aged and old animals. This age-dependent mRNA loss was paralleled by a marked reduction of alpha-synuclein protein; immunoreactivity of midbrain sections stained with an anti-alpha-synuclein antibody was most robust in 2-month-old mice and weakest in 20-month-old animals. Lowering of nigral alpha-synuclein could not be explained by a loss of dopaminergic neurons and was relatively specific since no change in beta-synuclein mRNA and protein occurred with advancing age. Finally, age-related decreases in alpha-synuclein were widespread throughout the mouse brain, affecting other regions (e.g., hippocampus) besides the substantia nigra. The data suggest that loss of alpha-synuclein could contribute to or be a marker of synaptic dysfunction in the aging brain. They also emphasize important differences in alpha-synuclein expression between rodents and primates since earlier reports have shown a marked elevation of alpha-synuclein protein in the substantia nigra of older humans and non-human primates. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/19800328/Decreased_alpha_synuclein_expression_in_the_aging_mouse_substantia_nigra_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(09)00408-7 DB - PRIME DP - Unbound Medicine ER -