title: Early onset of cognitive impairment is associated with altered synaptic plasticity and enhanced hippocampal GluA1 expression in a mouse model of depression.
abstract: 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 α-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 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated glutamatergic signaling.
authors: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel.
authors: Moshe
authors: M
authors: Gross
authors: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors: Anton
authors: A
authors: Sheinin
authors: Department of Molecular Biology, Ariel University, Ariel, Israel.
authors: Elimelech
authors: E
authors: Nesher
authors: Department of Molecular Biology, Ariel University, Ariel, Israel.
authors: Tatiana
authors: T
authors: Tikhonov
authors: Department of Molecular Biology, Ariel University, Ariel, Israel.
authors: Danny
authors: D
authors: Baranes
authors: Department of Molecular Biology, Ariel University, Ariel, Israel.
authors: Albert
authors: A
authors: Pinhasov
authors: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address: izhakm@post.tau.ac.il.
authors: Izhak
authors: I
authors: Michaelevski
mesh_terms: D000375:Aging; D000818:Animals; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D003863:Depression / Q000150:complications* / Q000523:psychology; D004195:Disease Models, Animal; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA
keywords: AMPAR; Depression; Hippocampus; Long-term potentiation; Memory; Submissiveness