Early onset of cognitive impairment is associated with altered synaptic plasticity and enhanced hippocampal GluA1 expression in a mouse model of depression.
Neurobiol Aging
; 36(5): 1938-52, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25796132
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trastornos del Conocimiento
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Receptores AMPA
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Depresión
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Hipocampo
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Plasticidad Neuronal
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Aging
Año:
2015
Tipo del documento:
Article
País de afiliación:
Israel