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

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Abstract

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.

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Acknowledgements

This work was supported by funds from the Ministerio de Economía y Competitividad (PSI2014-52660-R). The authors thank Dr. Jose Aguilera for his advice in conducting and interpreting the western blots data and Mr. Gerald-Patrick Fannon for his support with the English-language editing.

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Authors and Affiliations

  1. Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

    Marta Portero-Tresserra, Margarita Martí-Nicolovius, Mireia Tarrés-Gatius, Gemma Guillazo-Blanch & Anna Vale-Martínez

  2. Departament de Bioquímica i Biologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain

    Ana Candalija

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  1. Marta Portero-Tresserra
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Contributions

MPT, MMN, GGB, and AVM designed the experiments and wrote the manuscript. MPT, MMN, MTG, and AC conducted the experiments. MPT and MMN analyzed the data. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Margarita Martí-Nicolovius.

Ethics declarations

All procedures were carried out in compliance with the European Community Council Directive for care and use of laboratory animals (86/609/ECC) and with the Generalitat de Catalunya’s authorization (DOGC 2450 7/ 8/1997, DARP protocol number 3046).

Conflict of interest statement

All authors have contributed to the work and agree with the findings. This work has not been published before nor is it being considered for publication in another journal. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Portero-Tresserra, M., Martí-Nicolovius, M., Tarrés-Gatius, M. et al. Intra-hippocampal d-cycloserine rescues decreased social memory, spatial learning reversal, and synaptophysin levels in aged rats. Psychopharmacology 235, 1463–1477 (2018). https://doi.org/10.1007/s00213-018-4858-z

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