期刊
NEUROBIOLOGY OF AGING
卷 36, 期 5, 页码 1938-1952出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.02.015
关键词
Submissiveness; Memory; Depression; Hippocampus; Long-term potentiation; AMPAR
Memory deficit is a common manifestation of age-related cognitive impairment, of which depression is a frequently occurring comorbidity. Previously, we developed a submissive (Sub) mouse line, validated as a model of depressive-like behavior. Using learning paradigms testing hippocampus-dependent spatial and nonspatial memory, we demonstrate here that Sub mice developed cognitive impairments at earlier age (3 months), compared with wild-type mice. Furthermore, acute hippocampal slices from Sub animals failed to display paired-pulse facilitation, whereas primed burst stimulation elicited significantly enhanced long-term potentiation in region CA1, relative to control mice. Changes in synaptic plasticity were accompanied by markedly reduced hippocampal messenger RNA expression of insulin-like growth factor and brain-derived neurotrophic factor. Finally, we identified markedly elevated protein levels of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 in the hippocampi of Sub mice, which was exacerbated with age. Taken together, the results point to a linkage between depressive-like behavior and the susceptibility to develop age-related cognitive impairment, potentially by hippocampal a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated glutamatergic signaling. (C) 2015 Elsevier Inc. All rights reserved.
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