title: Increased expression of α-synuclein in aged human brain associated with neuromelanin accumulation.
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.
authors.affiliation: 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, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xuan
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Xu
authors.forename: De-Hong
authors.initials: DH
authors.lastname: Lu
authors.forename: Shun
authors.initials: S
authors.lastname: Yu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Kenji
authors.initials: K
authors.lastname: Uéda
authors.forename: Ye-Qing
authors.initials: YQ
authors.lastname: Cui
authors.forename: Bo-Yang
authors.initials: BY
authors.lastname: Zhang
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008543:Melanins / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D008543:Melanins; D051844:alpha-Synuclein; C014121:neuromelanin