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. 2003 Feb 3;456(2):176-83.
doi: 10.1002/cne.10525.

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

Scott E Hemby  1 , John Q Trojanowski, Stephen D Ginsberg
Affiliations

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

Scott E Hemby et al. J Comp Neurol. .

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 beta-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.

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Figures

Fig. 1
Fig. 1
Age-dependent assessment of DA receptor mRNA levels in hippocampal CA1 pyramidal neurons. mRNA expression values correspond to hybridization signal intensity for individual transcripts divided by the total blot hybridization signal intensity · 100. Symbols represent relative abundance of mRNAs for the transcripts for each subject.
Fig. 2
Fig. 2
Age-dependent assessment of DA receptor mRNA levels in EC layer II stellate cells. mRNA expression values correspond to hybridization intensity for individual transcripts divided by the total blot hybridization intensity · 100. Symbols represent relative abundance of mRNAs for the respective transcripts for each subject. In contrast to the case for CA1 pyramidal neurons, no significant age-related decrease in DA receptor expression was found.
Fig. 3
Fig. 3
Relationship of β-actin, 4Rtau, and 3Rtau mRNA expression in CA1 and stellate cells from EC layers II/III to age. Symbols represent relative abundance of mRNAs for the transcripts for each subject for CA1 (red dots) and EC layer II stellate cells (black dots).
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