Neuron-specific age-related decreases in dopamine receptor subtype mRNAs

• Type of Material: Article
• Authors: Scott E. Hemby, Emory University; John Q. Trojanowski, University of Pennsylvania; Stephen D. Ginsberg, New York University
• Language: English
• Date: 2003-02-03
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2002 Wiley-Liss, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/cne.10525/abstract;jsessionid=5FF0C1EACCF7991DE31D6E27B8CBA1A6.f01t01
• Title of Journal or Parent Work: Journal of Comparative Neurology
• ISSN: 0021-9967
• Volume: 456
• Issue: 2
• Start Page: 176
• End Page: 183
• Grant/Funding Information: Grant sponsor: National of Institute of Health; Grant number: DA013772; Grant number: NS043939; Grant number: AG10668; Grant number: AG09215; Grant number: AG10124; Grant sponsor: Stanley Foundation; Grant sponsor: Alliance for Autism Research; Grant sponsor: Alzheimer’s Association; Grant number: NIRG-00-2250.
• Keywords: aging; microarray; gene expression; hippocampus; entorhinal cortex
• Research Categories: Biology, Genetics; Biology, Neuroscience; Psychology, Physiological

Abstract

Age-related decline in dopamine receptor levels has been observed in regional studies of animal and human brains; however, identifying specific cellular substrates and/or alterations in distinct neuronal populations remains elusive. To evaluate whether age-related decreases in dopamine receptor subtypes are associated with specific cell populations in the hippocampus and entorhinal cortex, antisense RNA amplification was combined with cDNA array analysis to examine effects of aging on D1–D5 dopamine receptor mRNA expression levels in hippocampal CA1 pyramidal neurons and entorhinal cortex layer II stellate cells from post-mortem human brains (19–92 years). In CA1 pyramidal neurons, significant age-related decline was observed for dopamine receptor mRNAs (D1–D4, P < 0.001; D5, P < 0.05) but not for the cytoskeletal elements β-actin, three-repeat (3R) tau, and four-repeat (4R) tau. In contrast, no significant changes were observed in stellate cells across the same cohort. Thus, senescence may be a factor responsible for cell-specific decrements in dopamine receptor gene expression in one population of neurons within a circuit that is critical for learning and memory. Furthermore, these results support the hypothesis that alterations in dopaminergic function may also be related to behavioral abnormalities, such as psychosis, that occur with aging.