Increased d-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice

Francesco Errico, Robert Nisticò, Francesco Napolitano, Carmen Mazzola, Dalila Astone, Teresa Pisapia, Michela Giustizieri, Antimo D'Aniello, Nicola B. Mercuri, Alessandro Usiello

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Until recently, free d-amino acids were thought to be involved only in bacterial physiology. Nevertheless, today there is evidence that d-serine, by acting as co-agonist at NMDARs, plays a role in controlling neuronal functions in mammals. Besides d-serine, another d-amino acid, d-aspartate (d-Asp), is found in the mammalian brain with a temporal gradient of occurrence: high in embryo and low in adult. In this study, we demonstrate that d-Asp acts as an endogenous NMDAR agonist, since it triggers currents via interaction with each of NR2A-D receptor subunits. According to its pharmacological features, we showed that oral administration of d-Asp strongly enhances NMDAR-dependent LTP in adulthood and, in turn, completely rescues the synaptic plasticity decay observed in the hippocampus of aged animals. Therefore, our findings suggest a tantalizing hypothesis for which this in-embryo-occurring d-amino acid, when "forced" over its physiological content, may disclose plasticity windows inside which it counteracts the age-related reduction of NMDAR signaling.

Original languageEnglish
Pages (from-to)2229-2243
Number of pages15
JournalNeurobiology of Aging
Volume32
Issue number12
DOIs
Publication statusPublished - Dec 2011

Fingerprint

Neuronal Plasticity
Aspartic Acid
Amino Acids
Serine
Brain
Bacterial Physiological Phenomena
Embryonic Structures
Oral Administration
Mammals
Hippocampus
Pharmacology

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

Cite this

Errico, F., Nisticò, R., Napolitano, F., Mazzola, C., Astone, D., Pisapia, T., ... Usiello, A. (2011). Increased d-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. Neurobiology of Aging, 32(12), 2229-2243. https://doi.org/10.1016/j.neurobiolaging.2010.01.002

Increased d-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. / Errico, Francesco; Nisticò, Robert; Napolitano, Francesco; Mazzola, Carmen; Astone, Dalila; Pisapia, Teresa; Giustizieri, Michela; D'Aniello, Antimo; Mercuri, Nicola B.; Usiello, Alessandro.

In: Neurobiology of Aging, Vol. 32, No. 12, 12.2011, p. 2229-2243.

Research output: Contribution to journalArticle

Errico, F, Nisticò, R, Napolitano, F, Mazzola, C, Astone, D, Pisapia, T, Giustizieri, M, D'Aniello, A, Mercuri, NB & Usiello, A 2011, 'Increased d-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice', Neurobiology of Aging, vol. 32, no. 12, pp. 2229-2243. https://doi.org/10.1016/j.neurobiolaging.2010.01.002
Errico, Francesco ; Nisticò, Robert ; Napolitano, Francesco ; Mazzola, Carmen ; Astone, Dalila ; Pisapia, Teresa ; Giustizieri, Michela ; D'Aniello, Antimo ; Mercuri, Nicola B. ; Usiello, Alessandro. / Increased d-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 12. pp. 2229-2243.
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