N-Methylaspartate

Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one of the leading genetic causes of death in childhood. SMA is caused by a mutation of the survival-of-motor-neuron 1 (SMN1) gene, leading to a quantitative defect in the survival-motor-neuron (SMN) protein expression. All patients retain one or more copies of the SMN2 gene, which modulates the disease severity by producing a small amount of stable SMN protein.

Author(s): 
Branchu, Julien
Biondi, Olivier
Chali, Farah
Collin, Thibault
Leroy, Felix
Mamchaoui, Kamel
Makoukji, Joelle
Pariset, Claude
Lopes, Philippe
Massaad, Charbel
Chanoine, Christophe
Charbonnier, FrÈdÈric
Publication Title: 
Amino Acids

Glutamate, an excitatory amino acid, acts at several glutamate receptor subtypes. Recently, we reported that central administration of glutathione induced hypnosis under stressful conditions in neonatal chicks. Glutathione appears to bind to the N-methyl-D-aspartate (NMDA) receptor. To clarify the involvement of each glutamate receptor subtype during stressful conditions, intracerebroventricular (i.c.v.) injection of several glutamate receptor agonists was given to chicks under social separation stress. Glutamate dose-dependently induced a hypnotic effect.

Author(s): 
Yamane, H.
Tsuneyoshi, Y.
Denbow, D. M.
Furuse, M.
Publication Title: 
The American Journal of Chinese Medicine

In Ayurveda,Withania somnifera (WS) is used as a medicine to maintain mental and physical health as well as to enhance memory. In this study, the methanolic extract of WS(mWS) was tested for its electrical influence on hippocampal CA1 pyramidal neurons using a patch clamp technique. In current clamp mode under a high chloride pipette solution, mWS (400 ng/μl) induced remarkable membrane depolarization (9.75 ± 2.54 mV, n = 6) of CA1 neurons. The mWS-induced depolarization was dose-dependent, reproducible, and persistent in the presence of 0.5 μM tetrodotoxin (TTX, 10.17 ± 0.04 mV, n = 6).

Author(s): 
Bhattarai, Janardhan Prasad
Park, Soo Joung
Han, Seong Kyu
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities.

Author(s): 
Fairbanks, C. A.
Schreiber, K. L.
Brewer, K. L.
Yu, C. G.
Stone, L. S.
Kitto, K. F.
Nguyen, H. O.
Grocholski, B. M.
Shoeman, D. W.
Kehl, L. J.
Regunathan, S.
Reis, D. J.
Yezierski, R. P.
Wilcox, G. L.
Publication Title: 
British Journal of Pharmacology

1. We previously reported that four new phenylpropanoid glycosides and six known cinnamate derivatives isolated from roots of Scrophularia buergeriana Miquel (Scrophulariaceae) protected cultured cortical neurons from neurotoxicity induced by glutamate. Here, we have investigated the structure-activity relationships in the phenylpropanoids using our primary culture system. 2. The alpha,beta-unsaturated ester moiety and the para-methoxy group in the phenylpropanoids appeared to play a vital role in neuroprotective activity.

Author(s): 
Kim, So Ra
Sung, Sang Hyun
Jang, Young Pyo
Markelonis, George J.
Oh, Tae H.
Kim, Young Choong
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Huntington's disease (HD) is a fully penetrant autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in the Huntingtin gene. Transcriptional dysfunction, excitotoxicity, and oxidative stress have all been proposed to play important roles in the pathogenesis of HD. This study was designed to explore the therapeutic potential of mithramycin, a clinically approved guanosine-cytosine-rich DNA binding antitumor antibiotic.

Author(s): 
Ferrante, Robert J.
Ryu, Hoon
Kubilus, James K.
D'Mello, Santosh
Sugars, Katharine L.
Lee, Junghee
Lu, Peiyuan
Smith, Karen
Browne, Susan
Beal, M. Flint
Kristal, Bruce S.
Stavrovskaya, Irina G.
Hewett, Sandra
Rubinsztein, David C.
Langley, Brett
Ratan, Rajiv R.
Publication Title: 
Brain Research

Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to block GABA(A) receptors. The goal of this study was to test the potential role of a GABAergic mechanism for the neuroprotective activity of bilobalide. In rat hippocampal slices exposed to NMDA, release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of bilobalide (10 microM) and under low-chloride conditions.

Author(s): 
Kiewert, Cornelia
Kumar, Vikas
Hildmann, Oksana
Rueda, Misty
Hartmann, Joachim
Naik, Runa S.
Klein, Jochen
Publication Title: 
Neuroscience

Women have greater temporal summation of experimental pain stimuli and also have a higher propensity for developing chronic visceral pain conditions. Sex hormone-mediated regulation of N-methyl-d-aspartic acid receptors (NMDARs) in nociceptive pathways is a plausible mechanism that may underlie these phenomena. The aim of this study was to compare the effect of 17-beta-estradiol (E2) in modulation of NMDAR activity in adult male and female rat dorsal root ganglia (DRG) neurons. DRG neurons were collected from adult male or female rats and grown in short-term culture in steroid-free media.

Author(s): 
McRoberts, J. A.
Li, J.
Ennes, H. S.
Mayer, E. A.
Publication Title: 
Molecular Neurobiology

Alzheimer's disease (AD) is marked by an increase in the production of extracellular beta amyloid plaques and intracellular neurofibrillary tangles associated with a decline in brain function. Increases in oxidative stress are regarded as an early sign of AD pathophysiology, although the source of reactive oxygen species (ROS) and the mechanism(s) whereby beta amyloid peptides (Abeta) impact oxidative stress have not been adequately investigated.

Author(s): 
Simonyi, Agnes
He, Yan
Sheng, Wenwen
Sun, Albert Y.
Wood, W. Gibson
Weisman, Gary A.
Sun, Grace Y.
Publication Title: 
Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism

Epidemiologic studies have shown that foods rich in polyphenols, such as flavanols, can lower the risk of ischemic heart disease; however, the mechanism of protection has not been clearly established. In this study, we investigated whether epicatechin (EC), a flavanol in cocoa and tea, is protective against brain ischemic damage in mice. Wild-type mice pretreated orally with 5, 15, or 30 mg/kg EC before middle cerebral artery occlusion (MCAO) had significantly smaller brain infarcts and decreased neurologic deficit scores (NDS) than did the vehicle-treated group.

Author(s): 
Shah, Zahoor A.
Li, Rung-chi
Ahmad, Abdullah S.
Kensler, Thomas W.
Yamamoto, Masayuki
Biswal, Shyam
Doré, Sylvain

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