title: Aging elevates metabolic gene expression in brain cholinergic neurons.
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 (GABPalpha), 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.
authors.affiliation: Department of Molecular Pharmacology and Therapeutics, Mayo Clinic Jacksonville, Jacksonville, FL 32224, United States.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Baskerville
authors.forename: Caroline
authors.initials: C
authors.lastname: Kent
authors.forename: David
authors.initials: D
authors.lastname: Personett
authors.forename: Weil R
authors.initials: WR
authors.lastname: Lai
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.forename: Paul
authors.initials: P
authors.lastname: Coleman
authors.forename: Michael
authors.initials: M
authors.lastname: McKinney
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation
chemical_list: D009419:Nerve Tissue Proteins; D000109:Acetylcholine