ABSENCE OF AGE-RELATED CHANGES IN NIGRAL DOPAMINERGIC NEURONS OF ASIAN INDIANS: RELEVANCE TO LOWER INCIDENCE OF PARKINSON'S DISEASE

被引:51
作者
Alladi, P. A. [2 ]
Mahadevan, A. [3 ]
Yasha, T. C. [3 ]
Raju, T. R. [2 ]
Shankar, S. K. [3 ]
Muthane, U. [1 ]
机构
[1] Natl Inst Mental Hlth & Neurosci, Dept Neurol, Bangalore 560029, Karnataka, India
[2] Natl Inst Mental Hlth & Neurosci, Dept Neurophysiol, Bangalore 560029, Karnataka, India
[3] Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India
关键词
aging human substantia nigra; stereology and morphometry; melanized and non-melanized neurons; TH and Nurr1 immunohistochemistry; TUNEL staining; Asian Indians; SUBSTANTIA-NIGRA; RHESUS-MONKEY; TYROSINE-HYDROXYLASE; ALPHA-SYNUCLEIN; AUDITORY NUCLEI; PARS COMPACTA; CELL LOSS; NEUROMELANIN; EXPRESSION; MIDBRAIN;
D O I
10.1016/j.neuroscience.2008.11.051
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Age-related loss of melanized nigral neurons reported in the British Caucasians is not observed in Asian Indian, American and French adults. In the Americans, loss of dopaminergic phenotype occurs from midlife, without frank neurodegeneration. Here, we investigated whether nigral dopaminergic neurons in Asian Indians are lost with age or undergo morphological or biochemical dysfunction. Using unbiased stereology we estimated volume, number of melanized, borderline/non-melanized (n=34, 28 gestational weeks to 80 years) and tyrosine hydroxylase (TH)-Nurr1 co-labeled neurons (n=32, 28 gestational weeks to 80 years) in substantia nigra pars compacta. We quantified Nurr1 and TH proteins by immunoblotting (n=18, 28 gestational weeks to 69 years) and apoptotic neurons by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Nuclear and soma size was estimated by morphometry. There was no age-related decline in volume, neuronal density, neuronal numbers and TH-Nurr1 co-labeled neurons. TH and Nurr1 protein expression remained stable. Lack of TUNEL-TH co-labeled cells confirmed absence of neuronal apoptosis. The neuronal size remained unaltered. Our findings of preserved nigral dopaminergic neurons suggest no age-related loss of nigral function in Asian Indians, unlike the Americans. This may explain the lower incidence of Parkinson's disease in Asian Indians. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:236 / 245
页数:10
相关论文
共 38 条
[1]   Prenatal auditory enrichment with species-specific calls and sitar music modulates expression of Bcl-2 and Bax to alter programmed cell death in developing chick auditory nuclei [J].
Alladi, PA ;
Roy, T ;
Singh, N ;
Wadhwa, S .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2005, 23 (04) :363-373
[2]  
Anglade P, 1997, HISTOL HISTOPATHOL, V12, P25
[3]   Ageing of substantia nigra in humans: cell loss may be compensated by hypertrophy [J].
Cabello, CR ;
Thune, JJ ;
Pakkenberg, H ;
Pakkenberg, B .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2002, 28 (04) :283-291
[4]   NIGROSTRIATAL AND NIGROTHALAMIC FIBERS IN RHESUS-MONKEY [J].
CARPENTER, MB ;
PETER, P .
JOURNAL OF COMPARATIVE NEUROLOGY, 1972, 144 (01) :93-+
[5]   Age-associated increases of α-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion:: Is this the target for Parkinson's disease? [J].
Chu, Yaping ;
Kordower, Jeffrey H. .
NEUROBIOLOGY OF DISEASE, 2007, 25 (01) :134-149
[6]   Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra [J].
Chu, YP ;
Kompoliti, K ;
Cochran, EJ ;
Mufson, EJ ;
Kordower, JH .
JOURNAL OF COMPARATIVE NEUROLOGY, 2002, 450 (03) :203-214
[7]   ENDOCRINE AND NEUROGENIC REGULATION OF THE ORPHAN NUCLEAR RECEPTORS NUR77 AND NURR-1 IN THE ADRENAL-GLANDS [J].
DAVIS, IJ ;
LAU, LF .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (05) :3469-3483
[8]   THE HISTORY OF PARKINSONISM [J].
FAHN, S .
MOVEMENT DISORDERS, 1989, 4 :S2-S10
[9]   AGING AND PARKINSONS-DISEASE - SUBSTANTIA-NIGRA REGIONAL SELECTIVITY [J].
FEARNLEY, JM ;
LEES, AJ .
BRAIN, 1991, 114 :2283-2301
[10]   Neuromelanin in human dopamine neurons: Comparison with peripheral melanins and relevance to Parkinson's disease [J].
Fedorow, H ;
Tribl, F ;
Halliday, G ;
Gerlach, A ;
Riederer, P ;
Double, KL .
PROGRESS IN NEUROBIOLOGY, 2005, 75 (02) :109-124