d aspartate exerts an opposing role upon age dependent nmdar related synaptic plasticity and memory decay

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

N-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus Branchiostoma lanceolatum

<p>Abstract</p> <p>Background</p> <p>NMDA (<it>N</it>-methyl-D-aspartic acid) is a widely known agonist for a class of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong activity for the induction of hypothalamic factors and hypophyseal hormones in mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in the induction of GnRH (Gonadotropin Releasing Hormone) in the hypothalamus, and of LH (Luteinizing Hormone) and PRL (Prolactin) in the pituitary gland.</p> <p>Results</p> <p>In this study we show evidence for the occurrence of endogenous NMDA in the amphioxus <it>Branchiostoma lanceolatum</it>. A relatively high concentration of NMDA occurs in the nervous system of this species (3.08 ± 0.37 nmol/g tissue in the nerve cord and 10.52 ± 1.41 nmol/g tissue in the cephalic vesicle). As in rat, in amphioxus NMDA is also biosynthesized from D-aspartic acid (D-Asp) by a NMDA synthase (also called D-aspartate methyl transferase).</p> <p>Conclusion</p> <p>Given the simplicity of the amphioxus nervous and endocrine systems compared to mammalian, the discovery of NMDA in this protochordate is important to gain insights into the role of endogenous NMDA in the nervous and endocrine systems of metazoans and particularly in the chordate lineage.</p

D-Aspartic acid is a novel endogenous neurotransmitter

D-Aspartic acid (D-Asp) is present in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions and is implicated in nervous system development. We show here that D-Asp is a novel endogenous neurotransmitter in two distantly related animals, a mammal (Rattus norvegicus) and a mollusk (Loligo vulgaris). Our main findings demonstrate that D-Asp is present in high concentrations in the synaptic vesicles of axon terminals; synthesis for this amino acid occurs in neurons by conversion of L-Asp to D-Asp via D-aspartate racemase; depolarization of nerve endings with K+ ions evokes an immediate release of D-Asp in a Ca2+ dependent manner; specific receptors for D-Asp occur at the postsynaptic membrane, as demonstrated by binding assays and by the expansion of squid skin chromatophores; D-aspartate oxidase, the specific enzyme that oxidizes D-Asp, is present in the postsynaptic membranes; and stimulation of nerve endings with D-Asp triggers signal transduction by increasing the second messenger cAMP. Taken together, these data demonstrate that D-Asp fulfills all criteria necessary to be considered a novel endogenous neurotransmitter. Given its known role in neurogenesis, learning, and neuropathologies, our results have important implications for biomedical and clinical research.-D'Aniello, S., Somorjai, I., Garcia-Fernandez, J., Topo, E., D'Aniello, A. D-Aspartic acid is a novel endogenous neurotransmitter. FASEB J. 25, 1014-1027 (2011). www.fasebj.org</p

-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus -1

<p><b>Copyright information:</b></p><p>Taken from "-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus "</p><p>http://www.biomedcentral.com/1471-2202/8/109</p><p>BMC Neuroscience 2007;8():109-109.</p><p>Published online 20 Dec 2007</p><p>PMCID:PMC2241627.</p><p></p>before purification by OPA treatment. The same sample after purification with OPA, which eliminates all the amino acids (or almost all) except NMDA. Note that it is not possible to see the NMDA in this graphic because it does not react with OPA-mercaptoethanol, that is the reagent used for the determination of free amino acids at HPLC. The same sample as B, but after treatment with D-AspO. In this case, the D-AspO oxidizes NMDA producing the CHNHwhich reacts with OPA-mercaptoethanol to give a well-defined sharp peak at the end of the chromatogram at retention time 11.8–12.0 min

Oxidation reaction of NMDA by D-Aspartate oxidase and production of methylamine (CHNH)

<p><b>Copyright information:</b></p><p>Taken from "-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus "</p><p>http://www.biomedcentral.com/1471-2202/8/109</p><p>BMC Neuroscience 2007;8():109-109.</p><p>Published online 20 Dec 2007</p><p>PMCID:PMC2241627.</p><p></p