Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra. J Comp Neurol 2002 Aug 26;450(3):203-14
Date
09/05/2002Pubmed ID
12209851DOI
10.1002/cne.10261Scopus ID
2-s2.0-0037179121 (requires institutional sign-in at Scopus site) 170 CitationsAbstract
Nuclear receptor-related factor 1 (Nurr1), a member of the nuclear receptor superfamily, is associated with the induction of dopaminergic (DA) phenotypes in developing and mature midbrain neurons. It is well established that dopaminergic nigrostriatal function decreases with age. Whether age-related deficits in DA phenotypic markers are associated with alterations in Nurr1 expression is unknown. The present study found that virtually all of tyrosine hydroxylase-immunoreactive (TH-ir) neurons within the young adult human substantia nigra were Nurr1-immunoreactive (Nurr1-ir) positive. Stereologic counts revealed a significant reduction in the number of Nurr1-ir nigral neurons in middle-aged (23.13%) and aged (46.33%) individuals relative to young subjects. The loss of Nurr1-ir neurons was associated with a similar decline in TH-ir neuron number. In this regard, TH-ir neuronal number was decreased in middle-aged (11.10%) and in aged (45.97%) subjects, and this loss of TH-ir neurons was highly correlated (r = 0.92) with the loss of Nurr1-ir neurons. In contrast, the number of melanin-containing nigral neuron number was generally stable across age groups, indicating that changes in Nurr1 and TH reflect phenotypic age-related changes and not frank neuronal degeneration. In support of this concept, confocal microscopic analyses of Nurr1-ir and TH-ir fluorescence intensity revealed parallel decreases in Nurr1- and TH-immunofluorescence as a function of age. These data demonstrate that age-related decline of DA phenotypic markers is associated with down-regulation of Nurr1 expression in the SN.
Author List
Chu Y, Kompoliti K, Cochran EJ, Mufson EJ, Kordower JHAuthor
Elizabeth J. Cochran MD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Aging
Biomarkers
DNA-Binding Proteins
Dopamine
Down-Regulation
Female
Fluorescent Antibody Technique
Humans
Male
Middle Aged
Neurons
Nuclear Receptor Subfamily 4, Group A, Member 2
Parkinson Disease
Phenotype
Substantia Nigra
Synaptic Transmission
Transcription Factors
Transcription, Genetic
Tyrosine 3-Monooxygenase
