Increased D-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice.
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.
Errico
Francesco
F
CEINGE Biotecnologie Avanzate, Via Comunale Margherita, 482 - 80145, Naples, Italy.
Nisticò
Robert
R
Napolitano
Francesco
F
Mazzola
Carmen
C
Astone
Dalila
D
Pisapia
Teresa
T
Giustizieri
Michela
M
D'Aniello
Antimo
A
Mercuri
Nicola B
NB
Usiello
Alessandro
A
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D026603:D-Aspartic Acid / Q000378:metabolism / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D013569:Synapses / Q000469:parasitology / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
D026603:D-Aspartic Acid