title: Absence of age-related changes in nigral dopaminergic neurons of Asian Indians: relevance to lower incidence of Parkinson's disease.
abstract: 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.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore 560029, India. alladiphalguni@yahoo.com
authors.forename: P A
authors.initials: PA
authors.lastname: Alladi
authors.forename: A
authors.initials: A
authors.lastname: Mahadevan
authors.forename: T C
authors.initials: TC
authors.lastname: Yasha
authors.forename: T R
authors.initials: TR
authors.lastname: Raju
authors.forename: S K
authors.initials: SK
authors.lastname: Shankar
authors.forename: U
authors.initials: U
authors.lastname: Muthane
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D017209:Apoptosis / Q000502:physiology; D048429:Cell Size; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005333:Fetus; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D007194:India / Q000208:ethnology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012016:Reference Values; D013194:Staining and Labeling / Q000379:methods; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine