Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6810153 | Neurobiology of Aging | 2011 | 14 Pages |
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 (Ddoâ/â). Strikingly, we demonstrated that the enhancement of hippocampal synaptic plasticity and cognition in 4/5-month-old Ddoâ/â 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.
Related Topics
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Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Francesco Errico, Robert Nisticò, Francesco Napolitano, Alessandra Bonito Oliva, Rosaria Romano, Federica Barbieri, Tullio Florio, Claudio Russo, Nicola B. Mercuri, Alessandro Usiello,