Determination of d-aspartate N-methyltransferase activity in the starfish by direct analysis of N-methyl-d-aspartate with high-performance liquid chromatography

Shibata, Keitaro; Sugaya, Noriko; Ono, Wakana; Abe, Katsumasa; Takahashi, Shouji; Kera, Yoshio

doi:10.1016/j.jchromb.2011.02.035

Cited by 7 publications

(1 citation statement)

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“…NMDA has been detected in rat brain and neuroendocrine tissues (D’Aniello et al 2000a; D’Aniello et al 2000b) and in invertebrates (Sato et al 1987; Todoroki et al 1999; D’Aniello et al 2003; D’Aniello et al 2007b; Shibata et al 2011), although many locations with substantial D-Asp have little or no detectable levels of NMDA. There are cases where NMDA is formed from D-Asp via the enzymatic activity of D-Asp methyltransferase (or the so called NMDA synthetase), which transfers the methyl group of S-adenosyl-L-methionine to D-Asp for NMDA formation (D’Aniello et al 2000a; D’Aniello et al 2000b; Shibata et al 2011). Considering that DAspO also digests NMDA (D’Aniello et al 1993a; D’Aniello et al 1993c), and that NMDA is a well-documented agonist for NMDA receptors (Watkins and Jane 2006), perhaps NMDA is a key player in multiple signaling pathways.…”

Section: Molecular and Cellular Functions Of D-aspmentioning

confidence: 99%

d-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems

2012

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D-Aspartate (D-Asp) is an endogenous amino acid in the central nervous and reproductive systems of vertebrates and invertebrates. High concentrations of D-Asp are found in distinct anatomical locations, suggesting that it has specific physiological roles in animals. Many of the characteristics of D-Asp have been documented, including its tissue and cellular distribution, formation and degradation, as well as the responses elicited by D-Asp application. D-Asp performs important roles related to nervous system development and hormone regulation; in addition, it appears to act as a cell-to-cell signaling molecule. Recent studies have shown that D-Asp fulfills many, if not all, of the definitions of a classical neurotransmitter—that the molecule’s biosynthesis, degradation, uptake, and release take place within the presynaptic neuron, and that it triggers a response in the postsynaptic neuron after its release. Accumulating evidence suggests that these criteria are met by a heterogeneous distribution of enzymes for D-Asp’s biosynthesis and degradation, an appropriate uptake mechanism, localization within synaptic vesicles, and a postsynaptic response via an ionotropic receptor. Although D-Asp receptors remain to be characterized, the postsynaptic response of D-Asp has been studied and several L-glutamate receptors are known to respond to D-Asp. In this review we discuss the current status of research on D-Asp in neuronal and neuroendocrine systems, and highlight results that support D-Asp’s role as a signaling molecule.

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Section: Molecular and Cellular Functions Of D-aspmentioning

confidence: 99%

d-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems

2012

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d-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice

et al. 2016

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D-Aspartate (D-Asp) is a free D-amino acid detected in multiple brain regions and putative precursor of endogenous N-methyl-D-aspartate (NMDA) acting as agonist at NMDA receptors. In this study, we investigated whether D-Asp (20 mM) in drinking solution for 1 month affects pain responses and pain-related emotional, and cognitive behaviour in a model of neuropathic pain induced by the spared nerve injury (SNI) of the sciatic nerve in mice. SNI mice developed mechanical allodynia and motor coordination impairment 30 days after SNI surgery. SNI mice showed cognitive impairment, anxiety and depression-like behaviour, reduced sociability in the three chamber sociability paradigm, increased expression of NR2B subunit of NMDA receptor and Homer 1a in the medial prefrontal cortex (mPFC). The expression of (post synaptic density) PSD-95 and Shank 1was instead unaffected in the mPFC of the SNI mice. Treatment with D-Asp drinking solution, started right after the SNI (day 0), alleviated mechanical allodynia, improved cognition and motor coordination and increased social interaction. D-Asp also restored the levels of extracellular D-Asp, Homer 1a and NR2B subunit of the NMDA receptor to physiological levels and reduced Shank1 and PSD-95 protein levels in the mPFC. Amitriptyline, a tricyclic antidepressant used also to alleviate neuropathic pain in humans, reverted mechanical allodynia and cognitive impairment, and unlike D-Asp, was effective in reducing depression and anxiety-like behaviour in the SNI mice and increased PSD protein level. Altogether these findings demonstrate that D-Asp improves sensorial, motor and cognitive-like symptoms related to chronic pain possibly through glutamate neurotransmission normalization in neuropathic mice.

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