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D-aspartate exerts an opposing role upon age-dependent NMDAR-related synaptic plasticity and memory decay

Francesco Errico¹, Robert Nistico'², Antimo D'Aniello³, Sandra Sivilia⁴, Michela Giustizieri², Francesco Napolitano¹, Enza Topo³, Giorgio Bernardi², Laura Calza⁴, Nicola Mercuri², & Alessandro Usiello¹

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1. CEINGE - Biotecnologie Avanzate, Behavioural Neuroscience
2. IRCCS S. Lucia, Sezione Ricerche-Neurologia Sperimentale
3. Stazione Zoologica, Neurobiology
4. Universita' di Bologna

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Manuscript

Date:

Received 14 May 2008 19:45 UTC; Posted 15 May 2008

Subjects:

Genetics, Neuroscience

Tags:

• synaptic plasticity
• cognition
• neurobiology
• Aging

Abstract:

In the present study, we demonstrated that D-aspartate acts as an in vitro and in vivo neuromodulatory molecule upon hippocampal NMDAR transmission. Accordingly, we showed that this D-amino acid, widely expressed during embryonic phase, was able to strongly influence hippocampus-related functions at adulthood. Thus, while up-regulated levels of D-aspartate increased LTP and spatial memory in four-month old adult mice, the prolonged deregulation of this molecule in thirteen-month old animals induced a substantial acceleration of age-dependent decay of synaptic plasticity and cognitive functions. Moreover, we highlighted a role for D-aspartate in enhancing NMDAR-dependent synaptic plasticity through an inducible "turn-on/turn-off-like mechanism". Strikingly, we also showed that D-aspartate, when administered to aged mice, strongly rescued their physiological synaptic decay and attenuated their cognitive deterioration. In conclusion, our data suggest a tantalizing hypothesis for which this in-embryo-occurring D-amino acid, might disclose plasticity windows in the aging brain.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Errico, Francesco, Nistico’, Robert, D’Aniello, Antimo, Sivilia, Sandra, Giustizieri, Michela, Napolitano, Francesco, Topo, Enza, Bernardi, Giorgio, Calza, Laura, Mercuri, Nicola, and Usiello, Alessandro. D-aspartate exerts an opposing role upon age-dependent NMDAR-related synaptic plasticity and memory decay. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1891.1> (2008)

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