Intra-hippocampal d-cycloserine rescues decreased social memory, spatial learning reversal, and synaptophysin levels in aged rats

Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associate...

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Detalhes bibliográficos
Autores: Portero Tresserra, Marta|||0000-0003-4149-1339, Martí Nicolovius, Margarita|||0000-0002-8669-6285, Tarrés-Gatius, Mireia, Candalija Iserte, Ana|||0000-0002-5003-3789, Guillazo i Blanch, Gemma|||0000-0002-8297-7100, Vale Martínez, Anna|||0000-0001-7369-7134
Tipo de documento: artigo
Data de publicação:2018
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:266920
Acesso em linha:https://ddd.uab.cat/record/266920
https://dx.doi.org/urn:doi:10.1007/s00213-018-4858-z
Access Level:Acceso aberto
Palavra-chave:Cognitive enhancer
GluN1 subunit
Glutamate
Morris water maze
NMDA receptor
Social transmission of food preference
Synaptophysin
Ventral hippocampus
Descrição
Resumo:Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. Objectives and Methods: The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats. We investigated the effects of pre-training infusions of DCS (10 μg/hemisphere) in the ventral hippocampus on two hippocampal-dependent learning tasks, the social transmission of food preference (STFP), and the Morris water maze (MWM). Results: The results revealed that infusions of DCS administered before the acquisition sessions rescued deficits in the STFP retention and MWM reversal learning in old rats. DCS also significantly increased the hippocampal levels of synaptophysin in old rats, which correlated with STFP and MWM performance in all tests. Moreover, although the levels of the GluN1 subunit correlated with the MWM acquisition and reversal, DCS did not enhance the expression of such synaptic protein. Conclusions: The present behavioral results support the role of DCS as a cognitive enhancer and suggest that enhancing the function of NMDARs and synaptic plasticity in the hippocampus may be related to improvement in social memory and spatial learning reversal in aged animals.