Displaying publications 1 - 20 of 26 in total

Abstract:
Sort:
  1. Fulltext Prevalence and Factor Associated with Anti-N-Methyl-D-Aspartate Receptor Encephalitis Among Patients with Medical Conditions: A Systematic Review and Meta-Analysis
    Lee KW, Khan AHKY, Ching SM, Kumar SJ, Raj CLVP, Chia PK, et al.
    Neurol India, 2024 May 01;72(3):476-486.
    PMID: 39041960 DOI: 10.4103/neuroindia.NI_981_20
    BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune encephalitis due to immune production of anti-NMDAR antibodies against the NR1 subunit of the NMDA receptor which is present throughout the central nervous system. This condition had been reported to be prevalent in patients with certain medical conditions; however so far, there have been limited systematic reviews and meta-analyses on the prevalence and factors associated.

    OBJECTIVE: This study was to determine the prevalence and factors associated with anti-NMDAR encephalitis among affected patients.

    MATERIAL AND METHODS: The protocol of this study has been registered (2019: CRD42019142002) with the International Prospective Register of Systematic Reviews (PROSPERO). The primary outcome was the incidence or prevalence of anti-NMDAR encephalitis and secondary outcomes were factors associated with anti-NMDAR encephalitis.

    RESULTS: There were 11 studies and a total of 873 million patients taken from high-risk populations across 11 countries that were included in the primary analysis. The overall pooled prevalence of anti-NMDAR encephalitis among patients with medical conditions was 7.0% (95% CI = 4.4, 9.6). Those with first episode of psychosis or schizophrenia were at a higher risk of developing anti-NMDAR encephalitis with an odds ratio of 5.976 (95% CI = 1.122, 31.825).

    CONCLUSION: We found that almost one-tenth of patients with medical conditions had anti-NMDAR encephalitis; particularly those with first episode of psychosis or schizophrenia were among the high-risk medical conditions.

    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/immunology
  2. Fulltext Anti N-Methyl-D-Aspartate receptor encephalitis: An under-recognised cause of encephalitis
    Rajahram GS, Nadarajah R, Lim KS, Menon J
    Med J Malaysia, 2015 Dec;70(6):363-4.
    PMID: 26988212 MyJurnal
    Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is an immune mediated condition with characteristic clinical presentation. We report the first case from Borneo, Sabah and the use of electroconvulsive therapy (ECT) in treating recalcitrant psychiatrist symptoms associated with this condition.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  3. Fulltext Anti-NMDAR Encephalitis in Association with Herpes Simplex Virus and Viral and Bacterial Zoonoses
    Yan Hung SK, Hiew FL, Viswanathan S
    Ann Indian Acad Neurol, 2019 1 30;22(1):102-103.
    PMID: 30692769 DOI: 10.4103/aian.AIAN_232_18
    Multiple co-infections can predispose a patient to autoimmune encephalitis. Out of thirty cases of N-methyl-D-aspartate receptor (NMDAR) encephalitis seen at a single tertiary referral center, only two cases of co-infection with NMDAR encephalitis were identified. One of these cases was highly interesting due to the presence of more than one co-infections along with the presence of cortical dysfunction, seizures, and orofacial dyskinesias at the onset in a male in the absence of tumors, which was refractory to initial treatment.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  4. Neuroprotection by trans-resveratrol in rats with N-methyl-D-aspartate (NMDA)-induced retinal injury: Insights into the role of adenosine A1 receptors
    Abd Ghapor AA, Abdul Nasir NA, Iezhitsa I, Agarwal R, Razali N
    Neurosci Res, 2023 Aug;193:1-12.
    PMID: 36796452 DOI: 10.1016/j.neures.2023.02.004
    Adenosine A1 receptors (AA1R) have been shown to counteract N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitotoxicity. In the present study, we investigated the role of AA1R in neuroprotection by trans-resveratrol (TR) against NMDA-induced retinal injury. In total, 48 rats were divided into the following four groups: normal rats pretreated with vehicle; rats that received NMDA (NMDA group); rats that received NMDA after pretreatment with TR; and rats that received NMDA after pretreatment with TR and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an AA1R antagonist. Assessment of general and visual behaviour was performed using the open field test and two-chamber mirror test, respectively, on Days 5 and 6 post NMDA injection. Seven days after NMDA injection, animals were euthanized, and eyeballs and optic nerves were harvested for histological parameters, whereas retinae were isolated to determine the redox status and expression of pro- and anti-apoptotic proteins. In the present study, the retinal and optic nerve morphology in the TR group was protected from NMDA-induced excitotoxic damage. These effects were correlated with the lower retinal expression of proapoptotic markers, lipid peroxidation, and markers of nitrosative/oxidative stress. The general and visual behavioural parameters in the TR group showed less anxiety-related behaviour and better visual function than those in the NMDA group. All the findings observed in the TR group were abolished by administration of DPCPX.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  5. Fulltext 9th Workshop on the Neurobiology of Epilepsy (WONOEP IX): the transition from the interictal to the ictal state (Teluk Nibong, Langkawi Island, Malaysia, July 4-7, 2007)
    de Curtis M, Murashima Y, Sankar R
    Epilepsia, 2008 Aug;49(8):1475-9.
    PMID: 18754944 DOI: 10.1111/j.1528-1167.2008.01618_1.x
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/physiology*
  6. Methyl Palmitate Modulated NMDA-Induced Cerebral Hyperemia in Hypertensive Rats
    Hsu CK, Chang SJ, Lim LY, Chang HH, Shei-Dei Yang S
    J Vasc Res, 2023;60(3):137-147.
    PMID: 37285812 DOI: 10.1159/000529916
    N-methyl-D-aspartate (NMDA) receptors were found to be dysfunctional in hypertensive rats. Methyl palmitate (MP) has been shown to diminish the nicotine-induced increase in blood flow in the brainstem. The aim of this study was to determine how MP modulated NMDA-induced increased regional cerebral blood flow (rCBF) in normotensive (WKY), spontaneously hypertensive (SHR), and renovascular hypertensive (RHR) rats. The increase in rCBF after the topical application of experimental drugs was measured using laser Doppler flowmetry. Topical NMDA application induced an MK-801-sensitive increase in rCBF in anesthetized WKY rats, which was inhibited by MP pretreatments. This inhibition was prevented by pretreatment with chelerythrine (a PKC inhibitor). The NMDA-induced increase in rCBF was also inhibited by the PKC activator in a concentration-dependent manner. Neither MP nor MK-801 affected the increase in rCBF induced by the topical application of acetylcholine or sodium nitroprusside. Topical application of MP to the parietal cortex of SHRs, on the other hand, increased basal rCBF slightly but significantly. MP enhanced the NMDA-induced increase in rCBF in SHRs and RHRs. These results suggested that MP had a dual effect on the modulation of rCBF. MP appears to play a significant physiological role in CBF regulation.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/physiology
  7. Multi-faceted Anti-obesity Effects of N-Methyl-D-Aspartate (NMDA) Receptor Modulators: Central-Peripheral Crosstalk
    Shiromwar SS, Chidrawar VR, Singh S, Chitme HR, Maheshwari R, Sultana S
    J Mol Neurosci, 2024 Jan 19;74(1):13.
    PMID: 38240858 DOI: 10.1007/s12031-023-02178-z
    Hypothalamus is central to food intake and satiety. Recent data unveiled the expression of N-methyl-D-aspartate receptors (NMDAR) on hypothalamic neurons and their interaction with GABAA and serotoninergic neuronal circuits. However, the precise mechanisms governing energy homeostasis remain elusive. Notably, in females, the consumption of progesterone-containing preparations, such as hormonal replacement therapy and birth control pills, has been associated with hyperphagia and obesity-effects mediated through the hypothalamus. To elucidate this phenomenon, we employed the progesterone-induced obesity model in female Swiss albino mice. Four NMDAR modulators were selected viz. dextromethorphan (Dxt), minocycline, d-aspartate, and cycloserine. Obesity was induced in female mice by progesterone administration for 4 weeks. Mice were allocated into 7 groups, group-1 as vehicle control (arachis oil), group-2 (progesterone + arachis oil), and group-3 as positive-control (progesterone + sibutramine); other groups were treated with test drugs + progesterone. Various parameters were recorded like food intake, thermogenesis, serum lipids, insulin, AST and ALT levels, organ-to-body weight ratio, total body fat, adiposity index, brain serotonin levels, histology of liver, kidney, and sizing of fat cells. Dxt-treated group has shown a significant downturn in body weight (p 
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/metabolism
  8. GRIN2D variants in three cases of developmental and epileptic encephalopathy
    Tsuchida N, Hamada K, Shiina M, Kato M, Kobayashi Y, Tohyama J, et al.
    Clin Genet, 2018 12;94(6):538-547.
    PMID: 30280376 DOI: 10.1111/cge.13454
    N-methyl-d-aspartate (NMDA) receptors are glutamate-activated ion channels that are widely distributed in the central nervous system and essential for brain development and function. Dysfunction of NMDA receptors has been associated with various neurodevelopmental disorders. Recently, a de novo recurrent GRIN2D missense variant was found in two unrelated patients with developmental and epileptic encephalopathy. In this study, we identified by whole exome sequencing novel heterozygous GRIN2D missense variants in three unrelated patients with severe developmental delay and intractable epilepsy. All altered residues were highly conserved across vertebrates and among the four GluN2 subunits. Structural consideration indicated that all three variants are probably to impair GluN2D function, either by affecting intersubunit interaction or altering channel gating activity. We assessed the clinical features of our three cases and compared them to those of the two previously reported GRIN2D variant cases, and found that they all show similar clinical features. This study provides further evidence of GRIN2D variants being causal for epilepsy. Genetic diagnosis for GluN2-related disorders may be clinically useful when considering drug therapy targeting NMDA receptors.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/genetics*; Receptors, N-Methyl-D-Aspartate/chemistry
  9. Fulltext NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
    Rothan HA, Amini E, Faraj FL, Golpich M, Teoh TC, Gholami K, et al.
    Sci Rep, 2017 03 30;7:45540.
    PMID: 28358047 DOI: 10.1038/srep45540
    N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors*; Receptors, N-Methyl-D-Aspartate/metabolism
  10. Fulltext Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
    Wong JH, Muthuraju S, Reza F, Senik MH, Zhang J, Mohd Yusuf Yeo NAB, et al.
    Biomed Pharmacother, 2019 Feb;110:168-180.
    PMID: 30469081 DOI: 10.1016/j.biopha.2018.11.044
    Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/biosynthesis*; Receptors, N-Methyl-D-Aspartate/genetics
  11. Fulltext Tualang Honey Improves Memory and Prevents Hippocampal Changes in Prenatally Stressed Rats
    Abd Aziz CB, Hasim H, Zakaria R, Ahmad AH
    Turk J Pharm Sci, 2020 Dec 23;17(6):620-625.
    PMID: 33389951 DOI: 10.4274/tjps.galenos.2019.21548
    Objectives: This study investigated whether the alterations in memory and hippocampus morphology and levels of malondialdehyde (MDA) and N-methyl-D-aspartate (NMDA) receptor in the hippocampus of adult rats after prenatal stress could be prevented by administration of Tualang honey (TH).

    Materials and Methods: Twenty-four pregnant rats were randomly grouped into a control group (C), a stress group (S), and a stress group treated with TH. Eight male pups from each group were randomly chosen and they were sacrificed at eight or ten weeks of age following the novel object recognition test. Their brains were removed and histological changes and levels of MDA and NMDA receptors in the hippocampus were determined.

    Results: The offspring from TH group showed significantly increased preference index (p<0.05) with higher neuronal number compared to S group. A significantly lower level of MDA and NMDA receptors were shown in TH group (P<0.01; P<0.05 respectively) compared to S group. The parameters investigated were not significantly different between C and TH groups.

    Conclusion: The study has shown that memory alteration, changes in hippocampus histology, MDA and NMDA receptor levels could be prevented by TH administration during prenatal stress. The results suggest the beneficial effects of Tualang honey in prenatally stressed rat offspring.

    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  12. Fulltext Anti N-Methyl-D-Aspartate receptor encephalitis with ovarian teratoma: a dilemma in diagnosis
    Lee, CL, Zainuddin AA, Abdul Karim AK, Yulianty A, Law, ZK, Md.Isa N, et al.
    Journal of Surgical Academia, 2016;6(1):66-69.
    MyJurnal
    We report a rare case of altered mental status in a young patient with immature ovarian teratoma. A 22-year-old woman presented with seizures, hallucination, amnesia and orofacial dyskinesia. Examination and investigation revealed an ovarian massand asalphing-oophorectomy was performed. The histopathological examination result showed an immature teratoma grade 2 with thepresence of immature primitive glial tissue. Her CSF N-Methyl-D-Aspartic acid receptor (Anti-NMDAR) antibodytest was positive. N-Methyl-D-Aspartic acid receptor antibody associated limbic encephalitis is an autoimmune antibody-mediated neuropsychiatric disorder. Resection of the tumour and immunotherapy resulted in full recovery.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  13. Fulltext Zerumbone Modulates α2A-Adrenergic, TRPV1, and NMDA NR2B Receptors Plasticity in CCI-Induced Neuropathic Pain In Vivo and LPS-Induced SH-SY5Y Neuroblastoma In Vitro Models
    Chia JSM, Izham NAM, Farouk AAO, Sulaiman MR, Mustafa S, Hutchinson MR, et al.
    Front Pharmacol, 2020;11:92.
    PMID: 32194397 DOI: 10.3389/fphar.2020.00092
    Zerumbone has shown great potential in various pathophysiological models of diseases, particularly in neuropathic pain conditions. Further understanding the mechanisms of action is important to develop zerumbone as a potential anti-nociceptive agent. Numerous receptors and pathways function to inhibit and modulate transmission of pain signals. Previously, we demonstrated involvement of the serotonergic system in zerumbone's anti-neuropathic effects. The present study was conducted to determine zerumbone's modulatory potential involving noradrenergic, transient receptor potential vanilloid type 1 (TRPV1) and N-methyl-D-aspartate (NMDA) receptors in chronic constriction injury (CCI)-induced in vitro and lipopolysaccharide (LPS)-induced SH-SY5Y in vitro neuroinflammatory models. von Frey filament and Hargreaves plantar tests were used to assess allodynia and hyperalgesia in the chronic constriction injury-induced neuropathic pain mouse model. Involvement of specific adrenoceptors were investigated using antagonists- prazosin (α1-adrenoceptor antagonist), idazoxan (α2-adrenoceptor antagonist), metoprolol (β1-adrenoceptor antagonist), ICI 118,551 (β2-adrenoceptor antagonist), and SR 59230 A (β3-adrenoceptor antagonist), co-administered with zerumbone (10 mg/kg). Involvement of excitatory receptors; TRPV and NMDA were conducted using antagonists capsazepine (TRPV1 antagonist) and memantine (NMDA antagonist). Western blot was conducted to investigate the effect of zerumbone on the expression of α2A-adrenoceptor, TRPV1 and NMDA NR2B receptors in CCI-induced whole brain samples of mice as well as in LPS-induced SH-SY5Y neuroblastoma cells. Pre-treatment with α1- and α2-adrenoceptor antagonists significantly attenuated both anti-allodynic and anti-hyperalgesic effects of zerumbone. For β-adrenoceptors, only β2-adrenoceptor antagonist significantly reversed the anti-allodynic and anti-hyperalgesic effects of zerumbone. β1-adrenoceptor antagonist only reversed the anti-allodynic effect of zerumbone. The anti-allodynic and anti-hyperalgesic effects of zerumbone were both absent when TRPV1 and NMDA receptors were antagonized in both nociceptive assays. Zerumbone treatment markedly decreased the expression of α2A-adrenoceptor, while an up-regulation was observed of NMDA NR2B receptors. Expression of TRPV1 receptors however did not significantly change. The in vitro study, representing a peripheral model, demonstrated the reduction of both NMDA NR2B and TRPV1 receptors while significantly increasing α2A-adrenoceptor expression in contrast to the brain samples. Our current findings suggest that the α1-, α2-, β1- and β2-adrenoceptors, TRPV1 and NMDA NR2B are essential for the anti-allodynic and antihyperalgesic effects of zerumbone. Alternatively, we demonstrated the plasticity of these receptors through their response to zerumbone's administration.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  14. Chronic and acute ammonia toxicity in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti: brain ammonia and glutamine contents, and effects of methionine sulfoximine and MK801
    Ip YK, Leong MW, Sim MY, Goh GS, Wong WP, Chew SF
    J Exp Biol, 2005 May;208(Pt 10):1993-2004.
    PMID: 15879078
    The objective of this study was to elucidate if chronic and acute ammonia intoxication in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti, were associated with high levels of ammonia and/or glutamine in their brains, and if acute ammonia intoxication could be prevented by the administration of methionine sulfoximine [MSO; an inhibitor of glutamine synthetase (GS)] or MK801 [an antagonist of N-methyl D-aspartate type glutamate (NMDA) receptors]. For P. schlosseri and B. boddaerti exposed to sublethal concentrations (100 and 8 mmol l(-1) NH4Cl, respectively, at pH 7.0) of environmental ammonia for 4 days, brain ammonia contents increased drastically during the first 24 h, and they reached 18 and 14.5 micromol g(-1), respectively, at hour 96. Simultaneously, there were increases in brain glutamine contents, but brain glutamate contents were unchanged. Because glutamine accumulated to exceptionally high levels in brains of P. schlosseri (29.8 micromol g(-1)) and B. boddaerti (12.1 micromol g(-1)) without causing death, it can be concluded that these two mudskippers could ameliorate those problems associated with glutamine synthesis and accumulation as observed in patients suffering from hyperammonemia. P. schlosseri and B. boddaerti could tolerate high doses of ammonium acetate (CH3COONH4) injected into their peritoneal cavities, with 24 h LC50 of 15.6 and 12.3 micromol g(-1) fish, respectively. After the injection with a sublethal dose of CH3COONH4 (8 micromol g(-1) fish), there were significant increases in ammonia (5.11 and 8.36 micromol g(-1), respectively) and glutamine (4.22 and 3.54 micromol g(-1), respectively) levels in their brains at hour 0.5, but these levels returned to normal at hour 24. By contrast, for P. schlosseri and B. boddaerti that succumbed within 15-50 min to a dose of CH3COONH4 (15 and 12 micromol g(-1) fish, respectively) close to the LC50 values, the ammonia contents in the brains reached much higher levels (12.8 and 14.9 micromol g(-1), respectively), while the glutamine level remained relatively low (3.93 and 2.67 micromol g(-1), respectively). Thus, glutamine synthesis and accumulation in the brain was not the major cause of death in these two mudskippers confronted with acute ammonia toxicity. Indeed, MSO, at a dosage (100 microg g(-1) fish) protective for rats, did not protect B. boddaerti against acute ammonia toxicity, although it was an inhibitor of GS activities from the brains of both mudskippers. In the case of P. schlosseri, MSO only prolonged the time to death but did not reduce the mortality rate (100%). In addition, MK801 (2 microg g(-1) fish) had no protective effect on P. schlosseri and B. boddaerti injected with a lethal dose of CH3COONH4, indicating that activation of NMDA receptors was not the major cause of death during acute ammonia intoxication. Thus, it can be concluded that there are major differences in mechanisms of chronic and acute ammonia toxicity between brains of these two mudskippers and mammalian brains.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
  15. Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease
    Rosini M, Simoni E, Caporaso R, Basagni F, Catanzaro M, Abu IF, et al.
    Eur J Med Chem, 2019 Oct 15;180:111-120.
    PMID: 31301562 DOI: 10.1016/j.ejmech.2019.07.011
    N-methyl-d-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid β peptide (Aβ) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from Aβ neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 μM). In addition, at 10 μM concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate Aβ production, as revealed by the observed increase of the non-amyloidogenic sAPPα in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving Aβ burden and oxidative damage.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors*; Receptors, N-Methyl-D-Aspartate/metabolism
  16. Amperometric microbiosensor as an alternative tool for investigation of D-serine in brain
    Mohd Zain Z, Ab Ghani S, O'Neill RD
    Amino Acids, 2012 Nov;43(5):1887-94.
    PMID: 22865247 DOI: 10.1007/s00726-012-1365-0
    This paper discusses the application of a reagentless, selective microbiosensor as a useful alternative tool for monitoring D-serine in neural samples. The main components of the 125-μm-diameter disk biosensor were D-amino acid oxidase for D-serine sensitivity (linear region slope, 61 ± 7 μA cm(-2) mM(-1); limit of detection, 20 nM), and poly-phenylenediamine for rejection of electroactive interference. The response time of the biosensor was of the order of 1 s, ideal for 'real-time' monitoring, and detection of systemically administered D-serine in brain extracellular fluid is demonstrated. Exploitation of this probe might resolve queries involving regulation of D-serine in excitotoxicity, and modulation of N-methyl-D-aspartate receptor function by D-serine and glycine in the central nervous system.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/metabolism
  17. Fulltext DRD and GRIN2B polymorphisms and their association with the development of impulse control behaviour among Malaysian Parkinson's disease patients
    Zainal Abidin S, Tan EL, Chan SC, Jaafar A, Lee AX, Abd Hamid MH, et al.
    BMC Neurol, 2015;15:59.
    PMID: 25896831 DOI: 10.1186/s12883-015-0316-2
    Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson's disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate/genetics*
  18. Fulltext Possible Participation of Ionotropic Glutamate Receptors and l-Arginine-Nitric Oxide-Cyclic Guanosine Monophosphate-ATP-Sensitive K+ Channel Pathway in the Antinociceptive Activity of Cardamonin in Acute Pain Animal Models
    Pui Ping C, Akhtar MN, Israf DA, Perimal EK, Sulaiman MR
    Molecules, 2020 Nov 18;25(22).
    PMID: 33217904 DOI: 10.3390/molecules25225385
    The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9-4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  19. Alteration of plasma alanine, glutamate, and glycine Level: A potentiate manic episode of bipolar disorder
    Wan Nasru WN, Ab Razak A, Yaacob NM, Wan Azman WN
    Malays J Pathol, 2021 Apr;43(1):25-32.
    PMID: 33903302
    INTRODUCTION: The amino acids that function as co-agonists at the N-methyl-D-aspartate (NMDA) receptor have been investigated in bipolar disorder (BD). However, studies comparing amino acid levels in the plasma of BD patients with healthy controls have yielded inconsistent results. We, therefore, conducted a study in Hospital Universiti Sains Malaysia to determine the plasma levels of glutamate, glycine, and alanine in BD patients and compared them with the healthy controls.

    MATERIALS AND METHODS: An overnight fast of 10-hour plasma levels of glutamate, glycine, alanine, and tryptophan were measured in 83 bipolar patients, and were compared to a group of 82 healthy controls.

    RESULTS: The mean (SD) age of bipolar patients was 40.9 (12.1), while the mean (SD) age for control groups was 35.6 (7.7) years. The median (25th, 75th percentile) of glutamate and alanine levels in bipolar patients was 111.0 (65.0,176.0) and 530.0 (446.0,629.0), respectively, while the mean (SD) of glycine level in bipolar patients was 304.0 (98.1). Significant higher glutamate, glycine, and alanine levels were found in bipolar disorder patients in the manic episode as compared to the healthy controls.

    CONCLUSION: Although the exact relationship between peripheral NMDA receptor co-agonist levels in the pathogenesis of BD is not well understood, these findings should be explored and may enlighten some new paths for BD therapy which could reward the patients also clinicians.

    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
  20. Fulltext Effects of Tualang honey on pain behaviour and oxidative stress in the thalamus of prenatally stressed rat offspring
    Hidani Hasim, Che Badariah Abd Aziz, Siti Qusyasyiah Ahmad Suhaimi, Mahaneem Mohamed, Idris Long, Rahimah Zakaria
    Malaysian Journal of Medicine and Health Sciences, 2020;16(3):85-92.
    MyJurnal
    Introduction: Increased nociceptive responses were shown in the offspring of prenatally stressed rats. Reports have demonstrated the anti-nociceptive effects of Tualang honey in the rat offspring. The present study was done to de- termine whether the modulation of nociceptive behaviour by Tualang honey was mediated by modulating changes in the histology, oxidative stress parameters and N-methyl-D-aspartate (NMDA) receptors in the thalamus of the rat offspring. Methods: Eighteen Sprague Dawley pregnant rats were randomly assigned to control (C), stress (S) and stress-treated with Tualang honey (SH) groups. Stress was given in a form of restraint stress.Tualang honey was given to SH group from first day of pregnancy until delivery. Thirty-three adult male offspring were subjected to formalin test before they were sacrificed. Nociceptive behaviour score, number of neurons, level of oxidative stress parameters and NMDA receptors in the thalamus were analysed by using one-way ANOVA. Results: The study demonstrated a significant decrease in mean nociceptive behaviour score (p
    Matched MeSH terms: Receptors, N-Methyl-D-Aspartate
Related Terms
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links