d-aspartate

The Piezo1 mechanosensitive ion channel is abundant on several elements of the central nervous system including astrocytes. It has been already demonstrated that activation of these channels is able to elicit calcium waves on astrocytes, which contributes to the release of gliotransmitters. Astrocyte- and N-methyl-D-aspartate (NMDA) receptor-dependent slow inward currents (SICs) are hallmarks of astrocyte-neuron communication. These currents are triggered by glutamate released as gliotransmitter, which in turn activates neuronal NMDA receptors responsible for this inward current having slower kinetics than any synaptic events...

N -methyl-d-aspartate receptors (NMDARs) are the main class of ionotropic receptors for the excitatory neurotransmitter glutamate. They play a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of several subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, and excitotoxicity...

Cancer is a significant global health threat and a leading cause of death worldwide. Effective early-stage interventions, particularly surgery, can potentially cure many solid tumors. However, the risk of postoperative cancer recurrence remains high. Recent research highlights the influence of perioperative anesthetic and analgesic choices on the fate of residual cancer cells, potentially affecting recurrence risks. Among these agents, ketamine-a well-known anesthetic and analgesic-has garnered interest due to its antitumor properties, mainly through inhibiting the N-methyl-D-aspartate (NMDA) receptor found in various cancer tissues...

Recombinant tissue-type plasminogen activator (r-tPA/Actilyse) stands as the prevailing pharmacological solution for treating ischemic stroke patients, of whom because their endogenous circulating tPA alone is not sufficient to rescue reperfusion and to promote favorable outcome. Beyond the tPA contributed by circulating endothelial cells and hepatocytes, neurons also express tPA, sparking debates regarding its impact on neuronal fate ranging from pro-survival to neurotoxic properties. In order to investigate the role of neuronal tPA during brain injuries, we developed models leading to its conditional deletion in neurons, employing AAV9-pPlat-GFP and AAV9-pPlat-Cre-GFP along with tPA floxed mice...

BACKGROUND: We have reported neuro-inflammation is involved in radicular pain by enhancing the efficiency of pain synaptic transmission in spinal level. Recently, peers' studies have confirmed that magnesium deficiency leads to neuro-inflammation, thus contributes to memory and emotional deficits and pain hypersensitivity in antineoplastic agents treated rats. In this study, we explore the effect of oral application of magnesium-L-threonate (L-TAMS) in radicular pain induced by lumbar disc herniation (LDH) of rats and the possible mechanisms...

Voltage-gated calcium channels (VGCCs) are the major conduits for calcium ions (Ca2+ ) within excitable cells. Recent studies have highlighted the non-ionotropic functionality of VGCCs, revealing their capacity to activate intracellular pathways independently of ion flow. This non-ionotropic signaling mode plays a pivotal role in excitation-coupling processes, including gene transcription through excitation-transcription (ET), synaptic transmission via excitation-secretion (ES), and cardiac contraction through excitation-contraction (EC)...

N -methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. Uniquely, NMDARs composed of GluN1 and GluN3 are activated exclusively by glycine, the neurotransmitter conventionally mediating inhibitory signaling when it binds to pentameric glycine receptors. The GluN1-3 NMDARs are vital for regulating neuronal excitability, circuit function, and specific behaviors, yet our understanding of their functional mechanism at the molecular level has remained limited...

Treatment of resistant obsessive-compulsive disorder (OCD) typically results in insufficient symptom alleviation, and even long-term medication often fails to have the intended effect. Ketamine is a potent non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. Studies have shown that low-dose ketamine infusion results in a considerable reduction in obsessive-compulsive symptoms and a rapid resolution of suicidal ideation. This is a case report on the effect of intravenous ketamine infusion on a patient with resistant OCD and severe suicidal ideation...

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extrasynaptic N-methyl-D-aspartate receptors with the contribution of astrocytes. These events are significantly slower than the excitatory postsynaptic currents. Parameters of slow inward currents are determined by several factors including the mechanisms of astrocytic activation and glutamate release, as well as the diffusion pathways from the release site towards the extrasynaptic receptors...

Proper regulation of N-methyl-D-aspartate-type glutamate receptor (NMDA receptor) expression is responsible for excitatory synaptic functions in the mammalian brain. NMDA receptor dysfunction can cause various neuropsychiatric disorders and neurodegenerative diseases. Posttranslational protein S-palmitoylation, the covalent attachment of palmitic acid to intracellular cysteine residues via thioester bonds, occurs in the carboxyl terminus of GluN2B, which is the major regulatory NMDA receptor subunit. Mutations of three palmitoylatable cysteine residues in the membrane-proximal cluster of GluN2B to non-palmitoylatable serine (3CS) lead to the dephosphorylation of GluN2B Tyr1472 in the hippocampus and cerebral cortex, inducing a reduction in the surface expression of GluN2B-containig NMDA receptors...

The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium-independent transport of small neutral amino acids, including L-Alanine (L-Ala), Glycine (Gly), and D-Serine (D-Ser), within the central nervous system (CNS). D-Ser and Gly are two key endogenous glutamate co-agonists that activate N-methyl-d-aspartate (NMDA) receptors by binding to the allosteric site. Mice deficient in Asc-1 display severe symptoms such as tremors, ataxia, and seizures, leading to early postnatal death...

Alzheimer is an irreversible progressive neurodegenerative disease that causes failure of cerebral neurons and disability of the affected person to practice normal daily life activities. There is no concrete evidence to identify the exact reason behind the disease, so several relevant hypotheses emerged, highlighting many possible therapeutic targets, such as acetylcholinesterase, cholinergic receptors, N -methyl d-aspartate receptors, phosphodiesterase, amyloid β protein, protein phosphatase 2A, glycogen synthase kinase-3 beta, β-secretase, γ-secretase, α-secretase, serotonergic receptors, glutaminyl cyclase, tumor necrosis factor-α, γ-aminobutyric acid receptors, and mitochondria...

PURPOSE: N-methyl-D-aspartate (NMDA) receptors that are expressed by T-cells modulate T-cell proliferation, cytotoxicity and cell migration toward chemokines. Several studies have shown an anti-inflammatory effect of NMDA receptor antagonists. This study compares the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) in a topical formulation (gel) with the cyclooxygenase (COX) inhibitor diclofenac in a topical formulation (gel) in rats with arthritis induced by Freund's Complete Adjuvant (FCA)...

Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence of potent treatments available in the current medical landscape. A new brain-protective medication developed in China, Edaravone dexboeol (EDB), has shown promise due to its antioxidant and anti-inflammatory properties, albeit with a need for additional research to elucidate its role and mechanisms in VD contexts. In a research setup, a VD model was established utilizing Sprague-Dawley (SD) rats, subjected to permanent bilateral typical carotid artery occlusion (2VO)...

BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls...

Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM10 exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM10 on MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia-like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM10 to 3...

Spinocerebellar ataxia type 1 (SCA1) is a debilitating neurodegenerative disorder of the cerebellum and brainstem. Memantine has been proposed as a potential treatment for SCA1. It blocks N-methyl-D-aspartate (NMDA) receptors on neurons, reduces excitotoxicity and decreases neurodegeneration in Alzheimer models. However, in cerebellar neurodegenerative diseases, the potential value of memantine is still unclear. We investigated the effects of memantine on motor performance and synaptic transmission in the cerebellum in a mouse model where mutant ataxin 1 is specifically targeted to glia...

OBJECTIVE: We present the case of a patient with clinical and imaging features of sporadic Creutzfeldt-Jakob disease (sCJD) and positive IgLON5 antibodies (Abs) in the serum and CSF. CASE REPORT: A 66-year-old Chinese man presented to the hospital with a stroke-like episode, followed by rapidly progressive cognitive decline, mutism, and parkinsonism. The MRI results showed a cortical ribboning sign in diffusion-weighted MRI, periodic triphasic waves with a slow background in EEG, and positive protein 14-3-3 in CSF...

Epilepsy is a neurological disorder characterised by unprovoked, repetitive seizures caused by abnormal neuronal firing. The Wnt/β-Catenin signalling pathway is involved in seizure-induced neurogenesis, aberrant neurogenesis, neuroinflammation, and hyperexcitability associated with epileptic disorder. Wnt/β-Catenin signalling is crucial for early brain development processes including neuronal patterning, synapse formation, and N-methyl-d-aspartate receptor (NMDAR) regulation. Disruption of molecular networks such as Wnt/β-catenin signalling in epilepsy could offer encouraging anti-epileptogenic targets...

Homocysteine, a sulfur-containing amino acid derived from methionine metabolism, is a known agonist of N-methyl-D-aspartate receptor (NMDAR) and is involved in neurotoxicity. Our previous findings showed that neuronal exposure to elevated homocysteine levels leads to sustained low-level increase in intracellular Ca2+ , which is dependent on GluN2A subunit-containing NMDAR (GluN2A-NMDAR) stimulation. These studies further showed a role of ERK MAPK in homocysteine-GluN2A-NMDAR mediated neuronal death. However, the intracellular mechanisms associated with such sustained GluN2A-NMDAR stimulation and subsequent Ca2+ influx have remained unexplored...