1. Increased D-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice
- Author
-
Robert Nisticò, Carmen Mazzola, Francesco Errico, Dalila Astone, Nicola Biagio Mercuri, Antimo D'Aniello, Alessandro Usiello, Francesco Napolitano, Teresa Pisapia, Michela Giustizieri, Errico, Francesco, Robert, Nistic?, Napolitano, Francesco, Carmen, Mazzola, Dalila, Astone, Teresa, Pisapia, Michela, Giustizieri, Antimo, D?aniello, Nicola B., Mercuri, Alessandro, Usiello, Errico, F, Nisticò, R, Napolitano, F, Mazzola, C, Astone, D, Pisapia, T, Giustizieri, M, D'Aniello, A, Mercuri, Nb, and Usiello, Alessandro
- Subjects
Agonist ,Male ,Aging ,Maze Learning ,Animals ,Synapses ,Hippocampus ,Brain ,D-Aspartic Acid ,Exploratory Behavior ,Mice ,Excitatory Postsynaptic Potentials ,Mice, Inbred C57BL ,Up-Regulation ,Neuronal Plasticity ,medicine.drug_class ,Nonsynaptic plasticity ,Hippocampal formation ,Biology ,Inbred C57BL ,NMDA receptors ,Synaptic plasticity ,pathology/physiology, Animals, Brain ,metabolism/physiology, D-Aspartic Acid ,metabolism/physiology, Excitatory Postsynaptic Potentials ,physiology, Exploratory Behavior ,physiology, Hippocampus ,pathology/physiology, Male, Maze Learning ,physiology, Mice, Mice ,Inbred C57BL, Neuronal Plasticity ,physiology, Synapses ,parasitology/physiology, Up-Regulation ,physiology ,Metaplasticity ,D-Aspartete ,Brain aging ,reference memory ,medicine ,d-Aspartate ,General Neuroscience ,Settore BIO/14 ,Long-term potentiation ,NMDA receptor ,nervous system ,Neurology (clinical) ,Geriatrics and Gerontology ,Neuroscience ,Developmental Biology - 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."
- Published
- 2009