TY - JOUR
T1 - Intra-hippocampal d-cycloserine rescues decreased social memory, spatial learning reversal, and synaptophysin levels in aged rats
AU - Portero-Tresserra, Marta
AU - Martí-Nicolovius, Margarita
AU - Tarrés-Gatius, Mireia
AU - Candalija, Ana
AU - Guillazo-Blanch, Gemma
AU - Vale-Martínez, Anna
PY - 2018/5/1
Y1 - 2018/5/1
N2 - © 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Rationale: 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.
AB - © 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Rationale: 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.
KW - Cognitive enhancer
KW - GluN1 subunit
KW - Glutamate
KW - Morris water maze
KW - NMDA receptor
KW - Social transmission of food preference
KW - Synaptophysin
KW - Ventral hippocampus
UR - https://ddd.uab.cat/record/266920
UR - http://europepmc.org/abstract/med/29492616
U2 - 10.1007/s00213-018-4858-z
DO - 10.1007/s00213-018-4858-z
M3 - Article
C2 - 29492616
SN - 0033-3158
VL - 235
SP - 1463
EP - 1477
JO - Psychopharmacology
JF - Psychopharmacology
IS - 5
ER -