Persistent increase of d-aspartate in d-aspartate oxidase mutant mice induces a precocious hippocampal age-dependent synaptic plasticity and spatial memory decay

Francesco Errico, Robert Nisticò, Francesco Napolitano, Alessandra Bonito Oliva, Rosaria Romano, Federica Barbieri, Tullio Florio, Claudio Russo, Nicola B. Mercuri, Alessandro Usiello

Research output: Contribution to journalArticlepeer-review

Abstract

The atypical amino acid d-aspartate (d-Asp) occurs at considerable amounts in the developing brain of mammals. However, during postnatal life, d-Asp levels diminish following the expression of d-aspartate oxidase (DDO) enzyme. The strict control of DDO over its substrate d-Asp is particularly evident in the hippocampus, a brain region crucially involved in memory, and highly vulnerable to age-related deterioration processes. Herein, we explored the influence of deregulated higher d-Asp brain content on hippocampus-related functions during aging of mice lacking DDO (Ddo -/-). Strikingly, we demonstrated that the enhancement of hippocampal synaptic plasticity and cognition in 4/5-month-old Ddo -/- mice is followed by an accelerated decay of basal glutamatergic transmission, NMDAR-dependent LTP and hippocampus-related reference memory at 13/14 months of age. Therefore, the precocious deterioration of hippocampal functions observed in mutants highlights for the first time a role for DDO enzyme in controlling the rate of brain aging process in mammals.

Original languageEnglish
Pages (from-to)2061-2074
Number of pages14
JournalNeurobiology of Aging
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Brain aging
  • D-Aspartate
  • Hippocampus
  • NMDA receptors
  • Reference memory
  • Synaptic plasticity

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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