Aging elevates metabolic gene expression in brain cholinergic neurons

Karen A. Baskerville, Caroline Kent, David Personett, Weil R. Lai, Peter J. Park, Paul Coleman, Michael McKinney

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The basal forebrain (BF) cholinergic system is selectively vulnerable in human brain diseases, while the cholinergic groups in the upper pons of the brainstem (BS) resist neurodegeneration. Cholinergic neurons (200 per region per animal) were laser-microdissected from five young (8 months) and five aged (24 months) F344 rats from the BF and the BS pontine lateral dorsal tegmental/pedunculopontine nuclei (LDTN/PPN) and their expression profiles were obtained. The bioinformatics program SigPathway was used to identify gene groups and pathways that were selectively affected by aging. In the BF cholinergic system, aging most significantly altered genes involved with a variety of metabolic functions. In contrast, BS cholinergic neuronal age effects included gene groupings related to neuronal plasticity and a broad range of normal cellular functions. Transcription factor GA-binding protein alpha (GABPα), which controls expression of nuclear genes encoding mitochondrial proteins, was more strongly upregulated in the BF cholinergic neurons (+107%) than in the BS cholinergic population (+40%). The results suggest that aging elicits elevates metabolic activity in cholinergic populations and that this occurs to a much greater degree in the BF group than in the BS group.

Original languageEnglish (US)
Pages (from-to)1874-1893
Number of pages20
JournalNeurobiology of Aging
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2008

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Keywords

  • Acetylcholine
  • Aging
  • Basal forebrain
  • Bioinformatics
  • Gene expression
  • Metabolic genes
  • Neuronal vulnerability

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Baskerville, K. A., Kent, C., Personett, D., Lai, W. R., Park, P. J., Coleman, P., & McKinney, M. (2008). Aging elevates metabolic gene expression in brain cholinergic neurons. Neurobiology of Aging, 29(12), 1874-1893. https://doi.org/10.1016/j.neurobiolaging.2007.04.024