title: Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys.
abstract: Alterations in the basal forebrain cholinergic system have been widely studied in brain aging and Alzheimer's disease, but the magnitude of decline and relationship to cognitive impairment are still a matter of debate. The rhesus monkey (Macaca mulatta) provides a compelling model to study age-related memory decline, as the pattern of impairment closely parallels that observed in humans. Here, we used antibodies against the vesicular acetylcholine transporter and a new stereological technique to estimate total cholinergic fiber length in hippocampal subregions of behaviorally characterized young and aged rhesus monkeys. The analysis revealed an age-related decline in the length of cholinergic fibers of 22%, which was similar across the hippocampal subregions studied (dentate gyrus granule cell and molecular layers, CA2/3-hilus, and CA1), and across the rostral-caudal extent of the hippocampus. This effect, however, was unrelated to performance on the delayed nonmatching-to-sample task, a test of recognition memory sensitive to hippocampal system dysfunction and cognitive aging in monkeys. These findings indicate that a decline in cholinergic input fails to account for the influence of normal aging on memory supported by the primate hippocampal region.
authors.affiliation: Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology, Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Calhoun
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Peter R
authors.initials: PR
authors.lastname: Rapp
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000344:Afferent Pathways / Q000473:pathology* / Q000503:physiopathology; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D048429:Cell Size / Q000502:physiology; D002799:Cholinergic Fibers / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D026901:Membrane Transport Proteins; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D021641:Recognition, Psychology; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D026901:Membrane Transport Proteins; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D000109:Acetylcholine