Faculty Collaboration Database

Dopamine transporter-immunoreactive neurons decrease with age in the human substantia nigra. J Comp Neurol 1999 Jun 21;409(1):25-37

Date

06/11/1999

Pubmed ID

10363709

DOI

10.1002/(sici)1096-9861(19990621)409:1<25::aid-cne3>3.0.co;2-e

Scopus ID

2-s2.0-0033591617 (requires institutional sign-in at Scopus site)   122 Citations

Abstract

Unbiased disector stereologic cell counting was applied to sections from the human substantia nigra that were immunostained by using a monoclonal antibody against the dopamine transporter (DAT). This antibody was found to penetrate the full thickness of the stained section. Quantification of the number of DAT immunostained neurons was performed in human cases stratified into three age groups, young (ages 0-49 years), middle aged (ages 50-69 years), and aged (ages 70-85 years). The number of DAT-immunoreactive nigral neurons was normalized for each case by constructing a ratio of the number of DAT-containing neurons to total number of neuromelanin-containing cells in each subject's sample. Three types of DAT nigral neurons were seen: type 1, intensely stained; type 2, lightly stained; and type 3, DAT-immunonegative neuromelanin-containing perikarya. By 50 years of age, the number of type 1 neurons decreased significantly (P < 0.0001), whereas the number of type 2 neurons increased with age (P < 0.0001). Type 3 neurons also increased with age (P < 0.01), although less robustly than type 2 neurons. Type 1 neurons decreased by 11.2% per decade, and the total number of nigral neurons (types 1-3) decreased by 6.7% per decade. Relative to the young group, there were 75% and 88% reductions in type 1 neurons in the middle-aged and aged groups, respectively. This contrasts with the 35% and 41% reductions in total number of neuromelanin-containing neurons seen in middle-aged and aged groups, respectively. The young group had significantly more type 1 neurons and fewer type 2 neurons compared with middle-aged and aged participants. Post-hoc analyses indicated that the young group had significantly fewer type 3 neurons compared with middle-aged and aged participants. These findings demonstrate an age-related reduction in the number of substantia nigra DAT-immunoreactive neurons. Therefore, insight into the mechanisms regulating the rate of DAT synthesis may aid in our understanding of the decline of DATs with aging and its functional significance.

Author List

Ma SY, Ciliax BJ, Stebbins G, Jaffar S, Joyce JN, Cochran EJ, Kordower JH, Mash DC, Levey AI, Mufson EJ

Author

Elizabeth J. Cochran MD Adjunct Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Aging
Carrier Proteins
Child
Dopamine Plasma Membrane Transport Proteins
Female
Humans
Immunohistochemistry
Male
Membrane Glycoproteins
Membrane Transport Proteins
Middle Aged
Nerve Tissue Proteins
Neurons
Substantia Nigra