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Increase expression of α-synuclein in aged human brain associated with neuromelanin accumulation

Journal of Neural Transmission volume 118, pages 1575–1583 (2011)Cite this article

Abstract

Although the increased prevalence of Parkinson’s disease (PD) with aging suggests that aging processes predispose dopamine neurons to degeneration, the mechanism involved remains unknown. Dopamine neurons contain significant amounts of neuromelanin, and the amount of neuromelanin increases with aging. In the present study, age-related changes in the number of nigral neurons expressing neuromelanin (NM), α-synuclein, and tyrosine hydroxylase (TH) were stereologically analyzed in the postmortem brains of 28 healthy humans with an age range of 17–84 years. Stereological counting of NM content, α-synuclein content, and TH immunoreactivity revealed significant accumulation of NM and α-synuclein in neurons during the aging process. In cells containing a large amount of NM, α-synuclein-immunoreactive cells in aged individuals outnumbered those of younger individuals. In non-NM cells, the α-synuclein expression profile was similar across age groups. Furthermore, TH-immunoreactive neurons decreased significantly with aging, which was associated with accumulation of NM and α-synuclein. Our results suggest that age related accumulation of NM might induce α-synuclein over-expression and thereby make dopamine neurons more vulnerable to injuries.

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Acknowledgments

This study was supported by grants from the Major State Basic Research Development Program of China (973 program) (No. 2006CB500701), the National High Technology Research and Development Program of China (863 program) (No. 2006AA02A408), and the National Natural Science Foundation of China (No. 30671950, 30430280).

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Affiliations

  1. Department of Neurobiology and the Sino-Japan Joint Laboratory of Neurodegenerative diseases, Institute of Geriatrics of Beijing, Xuanwu Hospital of the Capital University of Medical Sciences, Key Laboratory for Neurodegenerative Disease of Ministry of Education, 45 Changchun Street, Beijing, 100053, China

    Qi Xuan, Sheng-Li Xu, Shun Yu, Ming Zhou, Kenji Uéda & Piu Chan

  2. Department of Pathology, Xuanwu Hospital of the Capital University of Medical Sciences, 45 Changchun Street, Beijing, 100053, China

    Qi Xuan & De-Hong Lu

  3. Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, 156-8585, Japan

    Kenji Uéda

  4. Department of General Surgery, Xuanwu Hospital of the Capital University of Medical Sciences, 45 Changchun Street, Beijing, 100053, China

    Ye-Qing Cui

  5. Forensic Medical Examination and Identification Center, Beijing Public Security Bureau, Beijing, 100085, China

    Bo-Yang Zhang

Authors
  1. Qi Xuan
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  2. Sheng-Li Xu
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  3. De-Hong Lu
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  4. Shun Yu
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  5. Ming Zhou
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  6. Kenji Uéda
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  7. Ye-Qing Cui
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  8. Bo-Yang Zhang
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  9. Piu Chan
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Corresponding author

Correspondence to Piu Chan.

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Q. Xuan and S.-L. Xu contributed equally to this work.

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Xuan, Q., Xu, SL., Lu, DH. et al. Increase expression of α-synuclein in aged human brain associated with neuromelanin accumulation. J Neural Transm 118, 1575–1583 (2011). https://doi.org/10.1007/s00702-011-0636-3

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  • DOI: https://doi.org/10.1007/s00702-011-0636-3

Keywords

  • Aging
  • α-Synuclein
  • Tyrosine hydroxylase
  • Neuromelanin