Transcriptional mechanisms of hippocampal aging.
Aging related cognitive decline is an increasing health problem but affects only a subset of elderly humans. This research uses outbred young (Y) and aged rats. Behavioral characterization distinguishes aged rats with impaired spatial learning (AI) and aged rats with unimpaired learning ability (AU), mimicking the varied susceptibility of the human population to age-associated learning impairment. Studies are testing a hypothesis that hippocampal transcriptional mechanisms and gene expression profiles linked to activator protein-1 (AP-1) and glucocorticoid receptor (GR), mineralocorticoid receptor (MR) or cyclic AMP response element binding protein (CREB) families of transcription factors distinguish successful or unsuccessful aging and cognition. Results from mRNA assays, in situ hybridization, electromobility shift assays and western immunoblot indicate changes in GR and CREB in AI rats. State of the art future approaches to define downstream transcription targets are described.
Lund
P Kay
PK
Department of Cell and Molecular Physiology, University of North Carolina, 6336 MBRB, 103 Mason Farm Road, CB# 7545, Chapel Hill, NC 27599-7545, USA. empk@med.unc.edu
Hoyt
Eileen C
EC
Bizon
Jennifer
J
Smith
Dani R
DR
Haberman
Rebecca
R
Helm
Kassie
K
Gallagher
Michela
M
D000375:Aging / Q000235:genetics*; D000818:Animals; D003071:Cognition / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D006624:Hippocampus / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D011965:Receptors, Glucocorticoid / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1