Age-associated alterations in hippocampal and basal forebrain nuclear factor kappa B activity.
Age-related cognitive deficits are often associated with loss of cholinergic activity within the neurotrophin-dependent cholinergic neurons that project from the basal forebrain to the hippocampus. The cause of reduced cholinergic function is unknown, but alterations in transcription factor-signaling pathways causing altered gene expression may cause decreased specific tissue function, resulting in loss of cholinergic activity. We measured transcription factor Nuclear Factor kappa B by electrophoretic mobility shift assay and Western analysis in young and aged rat brain tissues and report that basal levels of Nuclear Factor kappa B DNA-binding activity increase in the hippocampus and basal forebrain with age to significantly higher levels at 30 months of age. This age-associated increase in binding activity is associated with increased translocation of p65 to the nucleus. These data show an age-associated alteration in Nuclear Factor kappa B signal transduction pathways that may contribute to age-associated decreases in specific tissue function.
Toliver-Kinsky
T
T
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston 77555-0652, USA.
Papaconstantinou
J
J
Perez-Polo
J R
JR
D000344:Afferent Pathways / Q000378:metabolism; D000375:Aging / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D015398:Signal Transduction; D013312:Stress, Physiological / Q000378:metabolism; D014158:Transcription, Genetic
D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D004247:DNA