Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys.
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.
Calhoun
Michael E
ME
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.
Mao
Ying
Y
Roberts
Jeffrey A
JA
Rapp
Peter R
PR
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
D026901:Membrane Transport Proteins; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D000109:Acetylcholine