title: Secreted amyloid precursor protein-alpha can restore novel object location memory and hippocampal LTP in aged rats.
abstract: Secreted amyloid precursor protein-α (sAPPα) is a neurotrophic and neuroprotective molecule which can enhance learning and synaptic plasticity. Aging is associated with memory decline and impaired long-term potentiation (LTP). SAPPα therefore has potential as a nootropic agent which could be used to offset age-related cognitive decline. In this study we investigated the effects of sAPPα on spatial memory tasks and LTP in aged and young Long-Evans rats. Two hippocampus-dependent tasks were employed to measure spatial memory that is susceptible to impairments during aging. Aged rats showed a mild deficit in the novel object location task, but memory was significantly enhanced by bilateral intrahippocampal injections of sAPPα. There was no effect on the performance of young animals. In the watermaze task, however, sAPPα did not alleviate age-related decline in spatial memory. In subsequent electrophysiological experiments, LTP was impaired in slices from aged animals, but plasticity was rescued in a concentration-dependent manner by exogenous sAPPα administration. In contrast, LTP was impaired in young animals by sAPPα. Overall, these data support the hypothesis that sAPPα has therapeutic potential as a treatment for age-related cognitive decline.
authors: Department of Psychology, Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.
authors: Monica
authors: M
authors: Xiong
authors: Department of Psychology, Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.
authors: Owen D
authors: OD
authors: Jones
authors: Department of Biochemistry, Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.
authors: Katie
authors: K
authors: Peppercorn
authors: Department of Psychology, Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.
authors: Shane M
authors: SM
authors: Ohline
authors: Department of Biochemistry, Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.
authors: Warren P
authors: WP
authors: Tate
authors: Department of Psychology, Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin, New Zealand. Electronic address: cabraham@psy.otago.ac.nz.
authors: Wickliffe C
authors: WC
authors: Abraham
mesh_terms: D000375:Aging / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: Aging; Hippocampus; Long-term potentiation; Memory; Secreted amyloid precursor protein