Skip to content
2000
Volume 21, Issue 2
  • ISSN: 2666-0822
  • E-ISSN: 2666-0830

Abstract

The bidirectional communication among the different peptide neurotransmitters and their receptors influences brain, immunity, and behavior. Among the peptide neurotransmitters, Glutamate is the primary excitatory while; gamma-aminobutyrate (γ-GABA), is the inhibitory neurotransmitter. Glutamatergic/GABAergic imbalances are seen in many neurological and autoimmune disorders. With an aim to understand more deeply the intricacies of glutamate/GABA homeostasis, we provide a critical review of glutamate, glycine and GABA peptide neurotransmitters and their role in the brain, behavior, and immunity. Another aspect of maintaining this homeostasis has its origin in the gut-brain-axis which influences mood and behavior the bidirectional biochemical exchange network between central (CNS) and enteric nervous system (ENS). This present review also provides evidence of the cross-talk between glutamate, glycine, and GABA along the microbiota-gut-brain axis, thus any variations in this axis bear the consequences of the pathological condition. Drugs like alcohol, Benzodiazepines (Barbiturates) and neurosteroids inhibit the excitatory action of glutamate leading to an overall increase of glutamate/GABA ratio that causes relaxation of nerves. However, these drugs are misused and abused among drug addicts and now their commercial production is either banned or downsized and heavily monitored. Because only a limited number of drug molecules are considered in pharmaceutics and clinics as antidepressants, it is essential to focus on alternate peptide modulator analogues which are safe, eco-friendly and can be used as drugs to relieve stress and anxiety. In this review, we present a synopsis of the studies on synthetic GABAergic agonists or GABA modulators that can be targeted for future therapeutics and clinics.

Loading

Article metrics loading...

/content/journals/cprr/10.2174/0126660822262191231024081805
2025-05-01
2024-11-21
Loading full text...

Full text loading...

References

  1. LeeSH DanY Neuromodulation of brain states.neuron 2012761209222
    [Google Scholar]
  2. XiaX. WangY. QinY. ZhaoS. ZhengJ.C. Exosome: A novel neurotransmission modulator or non-canonical neurotransmitter?Ageing Res. Rev.20227410155810.1016/j.arr.2021.101558 34990846
    [Google Scholar]
  3. MastrangeloM. Epilepsy in inherited neurotransmitter disorders: Spotlights on pathophysiology and clinical management.Metab. Brain Dis.2021361294310.1007/s11011‑020‑00635‑x 33095372
    [Google Scholar]
  4. RosenbergR.N. PascualJ.M. Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease.Academic press20201
    [Google Scholar]
  5. BrennenstuhlH Jung-KlawitterS AssmannB OpladenT Inherited disorders of neurotransmitters: Classification and practical approaches for diagnosis and treatmentNeuropediatrics 20195010021410.1055/s‑0038‑1673630
    [Google Scholar]
  6. LepetaK. LourencoM.V. SchweitzerB.C. Synaptopathies: Synaptic dysfunction in neurological disorders: A review from students to students.J. Neurochem.2016138678580510.1111/jnc.13713 27333343
    [Google Scholar]
  7. TeleanuR.I. NiculescuA.G. RozaE. VladâcencoO. GrumezescuA.M. TeleanuD.M. Neurotransmitters—Key factors in neurological and neurodegenerative disorders of the central nervous system.Int. J. Mol. Sci.20222311595410.3390/ijms23115954 35682631
    [Google Scholar]
  8. ChenY. XuJ. ChenY. Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders.Nutrients2021136209910.3390/nu13062099 34205336
    [Google Scholar]
  9. HymanS.E. Neurotransmitters.Curr. Biol.2005155R154R15810.1016/j.cub.2005.02.037 15753022
    [Google Scholar]
  10. FosterJ.A. BakerG.B. DursunS.M. The relationship between the gut microbiome-immune system-brain axis and major depressive disorder.Front. Neurol.20211272112610.3389/fneur.2021.721126 34650506
    [Google Scholar]
  11. BelelliD. LambertJ.J. Neurosteroids: Endogenous regulators of the GABAA receptor.Nat. Rev. Neurosci.20056756557510.1038/nrn1703 15959466
    [Google Scholar]
  12. SegerstromS.C. MillerG.E. Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry.Psychol. Bull.2004130460163010.1037/0033‑2909.130.4.601 15250815
    [Google Scholar]
  13. WatkinsJC JaneDE The glutamate story.Br J Pharmacol2006147Suppl 1)(1S1008 16402093
    [Google Scholar]
  14. D’HulstC. AtackJ.R. KooyR.F. The complexity of the GABAA receptor shapes unique pharmacological profiles.Drug Discov. Today20091417-1886687510.1016/j.drudis.2009.06.009 19576998
    [Google Scholar]
  15. AprisonM.H. WermanR. The distribution of glycine in cat spinal cord and roots.Life Sci.19654212075208310.1016/0024‑3205(65)90325‑5 5866625
    [Google Scholar]
  16. AmthorF. Neuroscience for dummies.John Wiley & Sons2023
    [Google Scholar]
  17. WangW. WuZ. DaiZ. YangY. WangJ. WuG. Glycine metabolism in animals and humans: Implications for nutrition and health.Amino Acids201345346347710.1007/s00726‑013‑1493‑1 23615880
    [Google Scholar]
  18. SaransaariP. OjaS.S. Mechanisms of glycine release in mouse brain stem slices.Neurochem. Res.200934228629410.1007/s11064‑008‑9774‑x 18600448
    [Google Scholar]
  19. HübnerC.A. JentschT.J. Ion channel diseases.Hum. Mol. Genet.200211202435244510.1093/hmg/11.20.2435 12351579
    [Google Scholar]
  20. CurtisD.R. WatkinsJ.C. The excitation and depression of spinal neurones by structurally related amino acids.J. Neurochem.19606211714110.1111/j.1471‑4159.1960.tb13458.x 13718948
    [Google Scholar]
  21. HayashiT. Effects of sodium glutamate on the nervous system.Keio J. Med.19543418319210.2302/kjm.3.183
    [Google Scholar]
  22. MeldrumB.S. Glutamate as a neurotransmitter in the brain: Review of physiology and pathology.J. Nutr.20001304Suppl.1007S1015S10.1093/jn/130.4.1007S 10736372
    [Google Scholar]
  23. HollmannM. HeinemannS. Cloned glutamate receptors.Annu. Rev. Neurosci.19941713110810.1146/annurev.ne.17.030194.000335 8210177
    [Google Scholar]
  24. KeinänenK. WisdenW. SommerB. A family of AMPA-selective glutamate receptors.Science1990249496855656010.1126/science.2166337 2166337
    [Google Scholar]
  25. MonyerH. SprengelR. SchoepferR. Heteromeric NMDA receptors: Molecular and functional distinction of subtypes.Science199225650601217122110.1126/science.256.5060.1217 1350383
    [Google Scholar]
  26. NusserZ. LujanR. LaubeG. RobertsJ.D.B. MolnarE. SomogyiP. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus.Neuron199821354555910.1016/S0896‑6273(00)80565‑6 9768841
    [Google Scholar]
  27. ObrenovitchT.P. UrenjakJ. Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury?J. Neurotrauma1997141067769810.1089/neu.1997.14.677 9383088
    [Google Scholar]
  28. ConnP.J. PinJ.P. Pharmacology and functions of metabotropic glutamate receptors.Annu. Rev. Pharmacol. Toxicol.199737120523710.1146/annurev.pharmtox.37.1.205 9131252
    [Google Scholar]
  29. PinJ.P. DuvoisinR. The metabotropic glutamate receptors: Structure and functions.Neuropharmacology199534112610.1016/0028‑3908(94)00129‑G 7623957
    [Google Scholar]
  30. SchoeppD.D. ConnP.J. Metabotropic glutamate receptors in brain function and pathology.Trends Pharmacol. Sci.1993141132010.1016/0165‑6147(93)90107‑U 7680175
    [Google Scholar]
  31. BormannJ. The ‘ABC’ of GABA receptors.Trends Pharmacol. Sci.2000211161910.1016/S0165‑6147(99)01413‑3 10637650
    [Google Scholar]
  32. SteinV. NicollR.A. GABA generates excitement.Neuron200337337537810.1016/S0896‑6273(03)00056‑4 12575946
    [Google Scholar]
  33. BormannJ. FeigenspanA. GABAc receptors.Trends Neurosci.1995181251551910.1016/0166‑2236(95)98370‑E 8638289
    [Google Scholar]
  34. JohnstonG.A.R. GABAC receptors: Relatively simple transmitter-gated ion channels?Trends Pharmacol. Sci.199617931932310.1016/0165‑6147(96)10038‑9 8885697
    [Google Scholar]
  35. EnzR. CuttingG.R. Molecular composition of GABAC receptors.Vision Res.199838101431144110.1016/S0042‑6989(97)00277‑0 9667009
    [Google Scholar]
  36. SekirovI. RussellS.L. AntunesL.C.M. FinlayB.B. Gut microbiota in health and disease.Physiol. Rev.201090385990410.1152/physrev.00045.2009 20664075
    [Google Scholar]
  37. CarabottiM. SciroccoA. MaselliM.A. SeveriC. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems.Ann. Gastroenterol.2015282203209 25830558
    [Google Scholar]
  38. BajA. MoroE. BistolettiM. OrlandiV. CremaF. GiaroniC. Glutamatergic signaling along the microbiota-gut-brain axis.Int. J. Mol. Sci.2019206148210.3390/ijms20061482 30934533
    [Google Scholar]
  39. FondG. BoukouaciW. ChevalierG. The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic review.Pathol. Biol.2015631354210.1016/j.patbio.2014.10.003 25468489
    [Google Scholar]
  40. WangY. KasperL.H. The role of microbiome in central nervous system disorders.Brain Behav. Immun.20143811210.1016/j.bbi.2013.12.015 24370461
    [Google Scholar]
  41. VogtN.M. KerbyR.L. Dill-McFarlandK.A. Gut microbiome alterations in Alzheimer’s disease.Sci. Rep.2017711353710.1038/s41598‑017‑13601‑y 29051531
    [Google Scholar]
  42. BrandscheidC. SchuckF. ReinhardtS. Altered gut microbiome composition and tryptic activity of the 5xFAD Alzheimer’s mouse model.J. Alzheimers Dis.201756277578810.3233/JAD‑160926 28035935
    [Google Scholar]
  43. KellyJ.R. MinutoC. CryanJ.F. ClarkeG. DinanT.G. The role of the gut microbiome in the development of schizophrenia.Schizophr. Res.202123442310.1016/j.schres.2020.02.010 32336581
    [Google Scholar]
  44. ZhengP. ZengB. LiuM. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice.Sci. Adv.201952eaau831710.1126/sciadv.aau8317 30775438
    [Google Scholar]
  45. VuongH.E. HsiaoE.Y. Emerging roles for the gut microbiome in autism spectrum disorder.Biol. Psychiatry201781541142310.1016/j.biopsych.2016.08.024 27773355
    [Google Scholar]
  46. PeirceJ.M. AlviñaK. The role of inflammation and the gut microbiome in depression and anxiety.J. Neurosci. Res.201997101223124110.1002/jnr.24476 31144383
    [Google Scholar]
  47. MazzoliR. PessioneE. The neuro-endocrinological role of microbial glutamate and GABA signaling.Front. Microbiol.20167193410.3389/fmicb.2016.01934 27965654
    [Google Scholar]
  48. FilpaV. MoroE. ProtasoniM. CremaF. FrigoG. GiaroniC. Role of glutamatergic neurotransmission in the enteric nervous system and brain-gut axis in health and disease.Neuropharmacology2016111143310.1016/j.neuropharm.2016.08.024 27561972
    [Google Scholar]
  49. RooksM.G. GarrettW.S. Gut microbiota, metabolites and host immunity.Nat. Rev. Immunol.201616634135210.1038/nri.2016.42 27231050
    [Google Scholar]
  50. AgusA. PlanchaisJ. SokolH. Gut microbiota regulation of tryptophan metabolism in health and disease.Cell Host Microbe201823671672410.1016/j.chom.2018.05.003 29902437
    [Google Scholar]
  51. KaszakiJ. ÉrcesD. VargaG. SzabóA. VécseiL. BorosM. Kynurenines and intestinal neurotransmission: The role of N-methyl-d-aspartate receptors.J. Neural Transm.2012119221122310.1007/s00702‑011‑0658‑x 21617892
    [Google Scholar]
  52. Ramos-ChávezLA Lugo HuitrónR González EsquivelD Relevance of alternative routes of kynurenic acid production in the brain.Oxid med cell long2018201810.1155/2018/5272741
    [Google Scholar]
  53. Lugo-HuitrónR. Ugalde MuñizP. PinedaB. Pedraza-ChaverríJ. RíosC. Pérez-de la CruzV. Quinolinic acid: An endogenous neurotoxin with multiple targets.Oxid. Med. Cell. Long.20132013110402410.1155/2013/104024
    [Google Scholar]
  54. FrostG. SleethM.L. Sahuri-ArisoyluM. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism.Nat. Commun.201451361110.1038/ncomms4611 24781306
    [Google Scholar]
  55. GaoK. PiY. MuC.L. PengY. HuangZ. ZhuW.Y. Antibiotics-induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets.J. Neurochem.2018146321923410.1111/jnc.14333 29524228
    [Google Scholar]
  56. OtaruN. YeK. MujezinovicD. GABA production by human intestinal Bacteroides spp.: Prevalence, regulation, and role in acid stress tolerance.Front. Microbiol.20211265689510.3389/fmicb.2021.656895 33936013
    [Google Scholar]
  57. StrandwitzP. KimK.H. TerekhovaD. GABA-modulating bacteria of the human gut microbiota.Nat. Microbiol.20184339640310.1038/s41564‑018‑0307‑3 30531975
    [Google Scholar]
  58. BravoJ.A. ForsytheP. ChewM.V. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.Proc. Natl. Acad. Sci.201110838160501605510.1073/pnas.1102999108 21876150
    [Google Scholar]
  59. NewsholmeP. CuriR. Pithon CuriT.C. MurphyC.J. GarciaC. Pires de MeloM. Glutamine metabolism by lymphocytes, macrophages, and neutrophils: Its importance in health and disease.J. Nutr. Biochem.199910631632410.1016/S0955‑2863(99)00022‑4 15539305
    [Google Scholar]
  60. WangL. LiuY. ZhaoT.L. Topotecan induces apoptosis via ASCT2 mediated oxidative stress in gastric cancer.Phytomedicine20195711712810.1016/j.phymed.2018.12.011 30668314
    [Google Scholar]
  61. HaroonE. MillerA.H. SanacoraG. Inflammation, glutamate, and glia: A trio of trouble in mood disorders.Neuropsychopharmacology201742119321510.1038/npp.2016.199 27629368
    [Google Scholar]
  62. McCullumsmithR.E. SanacoraG. Regulation of extrasynaptic glutamate levels as a pathophysiological mechanism in disorders of motivation and addiction.Neuropsychopharmacology201540125425510.1038/npp.2014.218 25482181
    [Google Scholar]
  63. HardinghamG.E. BadingH. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders.Nat. Rev. Neurosci.2010111068269610.1038/nrn2911 20842175
    [Google Scholar]
  64. MalarkeyE.B. ParpuraV. Mechanisms of glutamate release from astrocytes.Neurochem. Int.2008521-214215410.1016/j.neuint.2007.06.005 17669556
    [Google Scholar]
  65. DumanR.S. Neurobiology of stress, depression, and rapid acting antidepressants: Remodeling synaptic connections.Depress. Anxiety201431429129610.1002/da.22227 24616149
    [Google Scholar]
  66. McEwenB.S. NascaC. GrayJ.D. Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex.Neuropsychopharmacology201641132310.1038/npp.2015.171 26076834
    [Google Scholar]
  67. ZhongZ. WheelerM.D. LiX. L-Glycine: A novel antiinflammatory, immunomodulatory, and cytoprotective agent.Curr. Opin. Clin. Nutr. Metab. Care20036222924010.1097/00075197‑200303000‑00013 12589194
    [Google Scholar]
  68. WheelerM.D. ThurmanR.G. Production of superoxide and TNF-α from alveolar macrophages is blunted by glycine.Am. J. Physiol.19992775L952L959 10564180
    [Google Scholar]
  69. El-HafidiM. FrancoM. RamírezA.R. Glycine increases insulin sensitivity and glutathione biosynthesis and protects against oxidative stress in a model of sucrose-induced insulin resistance.Oxid. Med. Cell. Longev.2018201811210.1155/2018/2101562 29675131
    [Google Scholar]
  70. JinZ. MenduS.K. BirnirB. GABA is an effective immunomodulatory molecule.Amino Acids2013451879410.1007/s00726‑011‑1193‑7 22160261
    [Google Scholar]
  71. (a LindquistC.E. BirnirB. Graded response to GABA by native extrasynaptic GABAA receptors.J. Neurochem.200697513491356
    [Google Scholar]
  72. (b BhatR. AxtellR. MitraA. Inhibitory role for GABA in autoimmune inflammation.Proc. Natl. Acad. Sci.2010107625802585 20133656
    [Google Scholar]
  73. OlsenR.W. SieghartW. GABAA receptors: Subtypes provide diversity of function and pharmacology.Neuropharmacology200956114114810.1016/j.neuropharm.2008.07.045 18760291
    [Google Scholar]
  74. MenduS.K. ÅkessonL. JinZ. Increased GABAA channel subunits expression in CD8+ but not in CD4+ T cells in BB rats developing diabetes compared to their congenic littermates.Mol. Immunol.201148439940710.1016/j.molimm.2010.08.005 21112637
    [Google Scholar]
  75. SoltaniN. QiuH. AleksicM. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes.Proc. Natl. Acad. Sci.201110828116921169710.1073/pnas.1102715108 21709230
    [Google Scholar]
  76. TianJ. DangH.N. YongJ. Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice.PLoS One201169e2533810.1371/journal.pone.0025338 21966503
    [Google Scholar]
  77. WheelerD.W. ThompsonA.J. CorlettoF. Anaesthetic impairment of immune function is mediated via GABA(A) receptors.PLoS One201162e1715210.1371/journal.pone.0017152 21390329
    [Google Scholar]
  78. PopovichP.G. LongbrakeE.E. Can the immune system be harnessed to repair the CNS?Nat. Rev. Neurosci.20089648149310.1038/nrn2398 18490917
    [Google Scholar]
  79. SchwartzM. ShechterR. Systemic inflammatory cells fight off neurodegenerative disease.Nat. Rev. Neurol.20106740541010.1038/nrneurol.2010.71 20531383
    [Google Scholar]
  80. CrowleyT. CryanJ.F. DownerE.J. O’LearyO.F. Inhibiting neuroinflammation: The role and therapeutic potential of GABA in neuro-immune interactions.Brain Behav. Immun.20165426027710.1016/j.bbi.2016.02.001 26851553
    [Google Scholar]
  81. GlaserR. RoblesT.F. SheridanJ. MalarkeyW.B. Kiecolt-GlaserJ.K. Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults.Arch. Gen. Psychiatry200360101009101410.1001/archpsyc.60.10.1009 14557146
    [Google Scholar]
  82. WinkelmanJ.W. BuxtonO.M. JensenJ.E. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS).Sleep200831111499150610.1093/sleep/31.11.1499 19014069
    [Google Scholar]
  83. ZhangC. HeJ. WangX. Dietary gamma-aminobutyric acid (GABA) improves non-specific immunity and alleviates lipopolysaccharide (LPS)-induced immune overresponse in juvenile Chinese mitten crab (Eriocheir sinensis).Fish Shellfish Immunol.202212448048910.1016/j.fsi.2022.04.028 35489590
    [Google Scholar]
  84. WeiH. ZouH. SheikhA.M. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation.J. Neuroinflammation2011815210.1186/1742‑2094‑8‑52 21595886
    [Google Scholar]
  85. HanS. TaiC. JonesC.J. ScheuerT. CatterallW.A. Enhancement of inhibitory neurotransmission by GABAA receptors having α2,3-subunits ameliorates behavioral deficits in a mouse model of autism.Neuron20148161282128910.1016/j.neuron.2014.01.016 24656250
    [Google Scholar]
  86. LiX. ChauhanA. SheikhA.M. Elevated immune response in the brain of autistic patients.J. Neuroimmunol.20092071-211111610.1016/j.jneuroim.2008.12.002 19157572
    [Google Scholar]
  87. PribiagH. StellwagenD. TNF-α downregulates inhibitory neurotransmission through protein phosphatase 1-dependent trafficking of GABA(A) receptors.J. Neurosci.20133340158791589310.1523/JNEUROSCI.0530‑13.2013 24089494
    [Google Scholar]
  88. MizunoT. ZhangG. TakeuchiH. Interferon‐γ directly induces neurotoxicity through a neuron specific, calcium‐permeable complex of IFN‐γ receptor and AMPA GluRl receptor.FASEB J.20082261797180610.1096/fj.07‑099499 18198214
    [Google Scholar]
  89. El-AnsaryA. Al-AyadhiL. GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders.J. Neuroinflammation201411118910.1186/s12974‑014‑0189‑0 25407263
    [Google Scholar]
  90. TianJ. DillionB.J. HenleyJ. ComaiL. KaufmanD.L. A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice.Front. Immunol.202213100795510.3389/fimmu.2022.1007955 36389819
    [Google Scholar]
  91. HanadaT. Ionotropic glutamate receptors in epilepsy: A review focusing on AMPA and NMDA receptors.Biomolecules202010346410.3390/biom10030464 32197322
    [Google Scholar]
  92. HarrisonP.J. LawA.J. EastwoodS.L. Glutamate receptors and transporters in the hippocampus in schizophrenia.Ann. N. Y. Acad. Sci.2003100319410110.1196/annals.1300.006 14684437
    [Google Scholar]
  93. ChanS.L. GriffinW.S.T. MattsonM.P. Evidence for caspase‐mediated cleavage of AMPA receptor subunits in neuronal apoptosis and Alzheimer’s disease.J. Neurosci. Res.199957331532310.1002/(SICI)1097‑4547(19990801)57:3<315::AID‑JNR3>3.0.CO;2‑# 10412022
    [Google Scholar]
  94. BlackM.D. Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data.Psychopharmacology2005179115416310.1007/s00213‑004‑2065‑6 15672275
    [Google Scholar]
  95. ChangP.K.Y. VerbichD. McKinneyR.A. AMPA receptors as drug targets in neurological disease: Advantages, caveats, and future outlook.Eur. J. Neurosci.201235121908191610.1111/j.1460‑9568.2012.08165.x 22708602
    [Google Scholar]
  96. CarrollR.C. LissinD.V. ZastrowM. NicollR.A. MalenkaR.C. Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures.Nat. Neurosci.19992545446010.1038/8123 10321250
    [Google Scholar]
  97. KristiansenL. HuertaI. BeneytoM. MeadorwoodruffJ. NMDA receptors and schizophrenia.Curr. Opin. Pharmacol.200771485510.1016/j.coph.2006.08.013 17097347
    [Google Scholar]
  98. ClintonS.M. Meador-WoodruffJ.H. Abnormalities of the NMDA receptor and associated intracellular molecules in the thalamus in schizophrenia and bipolar disorder.Neuropsychopharmacology20042971353136210.1038/sj.npp.1300451 15054476
    [Google Scholar]
  99. HeussC. ScanzianiM. GähwilerB.H. GerberU. G-protein-independent signaling mediated by metabotropic glutamate receptors.Nat. Neurosci.19992121070107710.1038/15996 10570483
    [Google Scholar]
  100. AbeT. SugiharaH. NawaH. ShigemotoR. MizunoN. NakanishiS. Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction.J. Biol. Chem.199226719133611336810.1016/S0021‑9258(18)42219‑3 1320017
    [Google Scholar]
  101. AramoriI. NakanishiS. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluRl, in transfected CHO cells.Neuron19928475776510.1016/0896‑6273(92)90096‑V 1314623
    [Google Scholar]
  102. ChavisP. ShinozakiH. BockaertJ. FagniL. The metabotropic glutamate receptor types 2/3 inhibit L-type calcium channels via a pertussis toxin-sensitive G-protein in cultured cerebellar granule cells.J. Neurosci.199414117067707610.1523/JNEUROSCI.14‑11‑07067.1994 7965099
    [Google Scholar]
  103. TanabeY. NomuraA. MasuM. ShigemotoR. MizunoN. NakanishiS. Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4.J. Neurosci.19931341372137810.1523/JNEUROSCI.13‑04‑01372.1993 8463825
    [Google Scholar]
  104. BrunoV. BattagliaG. CopaniA. Activation of class II or III metabotropic glutamate receptors protects cultured cortical neurons against excitotoxic degeneration.Eur. J. Neurosci.1995791906191310.1111/j.1460‑9568.1995.tb00712.x 8528465
    [Google Scholar]
  105. BrunoV. CopaniA. KnöpfelT. Activation of metabotropic glutamate receptors coupled to inositol phospholipid hydrolysis amplifies NMDA-induced neuronal degeneration in cultured cortical cells.Neuropharmacology19953481089109810.1016/0028‑3908(95)00077‑J 8532158
    [Google Scholar]
  106. SwansonC.J. BuresM. JohnsonM.P. LindenA.M. MonnJ.A. SchoeppD.D. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders.Nat. Rev. Drug Discov.20054213114410.1038/nrd1630 15665858
    [Google Scholar]
  107. KurczynskiT.W. Hyperekplexia.Arch. Neurol.198340424624810.1001/archneur.1983.04050040076015 6830476
    [Google Scholar]
  108. ShiangR. RyanS.G. ZhuY.Z. HahnA.F. O’ConnellP. WasmuthJ.J. Mutations in the α1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia.Nat. Genet.19935435135810.1038/ng1293‑351 8298642
    [Google Scholar]
  109. Al-OwainM. ColakD. Al-BakheetA. Novel mutation in GLRB in a large family with hereditary hyperekplexia.Clin. Genet.201281547948410.1111/j.1399‑0004.2011.01661.x 21391991
    [Google Scholar]
  110. SuhrenO. BruynG.W. TuynmanJ.A. Hyperexplexia.J. Neurol. Sci.19663657760510.1016/0022‑510X(66)90047‑5
    [Google Scholar]
  111. BakkerM.J. van DijkJ.G. van den MaagdenbergA.M.J.M. TijssenM.A.J. Startle syndromes.Lancet Neurol.20065651352410.1016/S1474‑4422(06)70470‑7 16713923
    [Google Scholar]
  112. HoonM. SoykanT. FalkenburgerB. Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina.Proc. Natl. Acad. Sci.201110873053305810.1073/pnas.1006946108 21282647
    [Google Scholar]
  113. VaroqueauxF. AramuniG. RawsonR.L. Neuroligins determine synapse maturation and function.Neuron200651674175410.1016/j.neuron.2006.09.003 16982420
    [Google Scholar]
  114. JamainS. QuachH. BetancurC. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.Nat. Genet.2003341272910.1038/ng1136 12669065
    [Google Scholar]
  115. PilorgeM. FassierC. Le CorroncH. Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism.Mol. Psychiatry201621793694510.1038/mp.2015.139 26370147
    [Google Scholar]
  116. LynchJW CallisterRJ Glycine receptors: A new therapeutic target in pain pathways.Curr opin investig drug2006714853
    [Google Scholar]
  117. EichlerS.A. FörsteraB. SmolinskyB. Splice-specific roles of glycine receptor α3 in the hippocampus.Eur. J. Neurosci.20093061077109110.1111/j.1460‑9568.2009.06903.x 19723286
    [Google Scholar]
  118. EichlerS.A. MeierJ.C. E-I balance and human diseases: From molecules to networking.Front. Mol. Neurosci.20081210.3389/neuro.02.002.2008 18946535
    [Google Scholar]
  119. JakobsC. BojaschM. MönchE. RatingD. SiemesH. HanefeldF. Urinary excretion of gamma-hydroxybutyric acid in a patient with neurological abnormalities. The probability of a new inborn error of metabolism.Clin. Chim. Acta19811112-316917810.1016/0009‑8981(81)90184‑4 7226548
    [Google Scholar]
  120. PearlP.L. GibsonK.M. AcostaM.T. Clinical spectrum of succinic semialdehyde dehydrogenase deficiency.Neurology20036091413141710.1212/01.WNL.0000059549.70717.80 12743223
    [Google Scholar]
  121. JaekenJ. CasaerP. de CockP. Gamma-aminobutyric acid-transaminase deficiency: A newly recognized inborn error of neurotransmitter metabolism.Neuropediatrics198415316516910.1055/s‑2008‑1052362 6148708
    [Google Scholar]
  122. ParvizM. VogelK. GibsonK. PearlP. Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies.J. Pediatr. Epilepsy20153421722710.3233/PEP‑14097 25485164
    [Google Scholar]
  123. TreimanD.M. GABAergic mechanisms in epilepsy.Epilepsia200142381210.1046/j.1528‑1157.2001.042suppl.3008.x 11520315
    [Google Scholar]
  124. LydiardR.B. The role of GABA in anxiety disorders.J. Clin. Psychiatry20036432127 12662130
    [Google Scholar]
  125. KalueffA.V. NuttD.J. Role of GABA in anxiety and depression.Depress. Anxiety200724749551710.1002/da.20262 17117412
    [Google Scholar]
  126. CarlssonA. WatersN. Holm-WatersS. TedroffJ. NilssonM. CarlssonM.L. Interactions between monoamines, glutamate, and GABA in schizophrenia:New evidence.Annu. Rev. Pharmacol. Toxicol.200141123726010.1146/annurev.pharmtox.41.1.237 11264457
    [Google Scholar]
  127. BlumB.P. MannJ.J. The GABAergic system in schizophrenia.Int. J. Neuropsychopharmacol.20025215917910.1017/S1461145702002894 12135541
    [Google Scholar]
  128. CoghlanS. HorderJ. InksterB. MendezM.A. MurphyD.G. NuttD.J. GABA system dysfunction in autism and related disorders: From synapse to symptoms.Neurosci. Biobehav. Rev.20123692044205510.1016/j.neubiorev.2012.07.005 22841562
    [Google Scholar]
  129. JoS. YarishkinO. HwangY.J. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease.Nat. Med.201420888689610.1038/nm.3639 24973918
    [Google Scholar]
  130. van NulandA.J.M. den OudenH.E.M. ZachH. GABAergic changes in the thalamocortical circuit in Parkinson’s disease.Hum. Brain Mapp.20204141017102910.1002/hbm.24857 31721369
    [Google Scholar]
  131. MaoX. MaoX. StanfordA.D. Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.Arch. Gen. Psychiatry201269544945910.1001/archgenpsychiatry.2011.1519 22213769
    [Google Scholar]
  132. JaphaK. KochM. Picrotoxin in the medial prefrontal cortex impairs sensorimotor gating in rats: reversal by haloperidol.Psychopharmacology1999144434735410.1007/s002130051017 10435407
    [Google Scholar]
  133. MizukamiK. SasakiM. IshikawaM. Immunohistochemical localization of γ-aminobutyric acidB receptor in the hippocampus of subjects with schizophrenia.Neurosci. Lett.2000283210110410.1016/S0304‑3940(00)00939‑3 10739885
    [Google Scholar]
  134. SimpsonM.D.C. SlaterP. DeakinJ.F.W. RoystonM.C. SkanW.J. Reduced GABA uptake sites in the temporal lobe in schizophrenia.Neurosci. Lett.19891071-321121510.1016/0304‑3940(89)90819‑7 2616032
    [Google Scholar]
  135. PettyF. KramerG.L. GullionC.M. John RushA. Low plasma γ-aminobutyric acid levels in male patients with depression.Biol. Psychiatry199232435436310.1016/0006‑3223(92)90039‑3 1420649
    [Google Scholar]
  136. PettyF. Plasma concentrations of gamma-aminobutyric acid (GABA) and mood disorders: A blood test for manic depressive disease?Clin. Chem.199440229630210.1093/clinchem/40.2.296 8313610
    [Google Scholar]
  137. BhagwagarZ. WylezinskaM. JezzardP. Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients.Int. J. Neuropsychopharmacol.200811225526010.1017/S1461145707007924 17625025
    [Google Scholar]
  138. BradyR.O.Jr McCarthyJ.M. PrescotA.P. Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder.Bipolar Disord.201315443443910.1111/bdi.12074 23634979
    [Google Scholar]
  139. GoddardA.W. MasonG.F. AlmaiA. Reductions in occipital cortex GABA levels in panic disorder detected with 1h-magnetic resonance spectroscopy.Arch. Gen. Psychiatry200158655656110.1001/archpsyc.58.6.556 11386984
    [Google Scholar]
  140. MöhlerH. The GABA system in anxiety and depression and its therapeutic potential.Neuropharmacology2012621425310.1016/j.neuropharm.2011.08.040 21889518
    [Google Scholar]
  141. SackeimH.A. DecinaP. ProhovnikI. MalitzS. ResorS.R. Anticonvulsant and antidepressant properties of electroconvulsive therapy: A proposed mechanism of action.Biol. Psychiatry1983181113011310 6317065
    [Google Scholar]
  142. BhagwagarZ. WylezinskaM. TaylorM. JezzardP. MatthewsP.M. CowenP.J. Increased brain GABA concentrations following acute administration of a selective serotonin reuptake inhibitor.Am. J. Psychiatry2004161236837010.1176/appi.ajp.161.2.368 14754790
    [Google Scholar]
  143. HaefelyW. KulcsárA. MöhlerH. PieriL. PolcP. SchaffnerR. Possible involvement of GABA in the central actions of benzodiazepines.Adv. Biochem. Psychopharmacol.197514131151 242199
    [Google Scholar]
  144. ChenH.Y. AlbertsonT.E. OlsonK.R. Treatment of drug-induced seizures.Br. J. Clin. Pharmacol.201681341241910.1111/bcp.12720 26174744
    [Google Scholar]
  145. BergmannK.J. Progabide.Clin. Neuropharmacol.198581132610.1097/00002826‑198503000‑00002 2983890
    [Google Scholar]
  146. Krogsgaard-LarsenP. FalchE. LarssonO.M. SchousboeA. GABA uptake inhibitors: Relevance to antiepileptic drug research.Epilepsy Res.198712779310.1016/0920‑1211(87)90012‑X 2973980
    [Google Scholar]
  147. MitaniH. ShirayamaY. YamadaT. MaedaK. AshbyC.R.Jr KawaharaR. Correlation between plasma levels of glutamate, alanine and serine with severity of depression.Prog. Neuropsychopharmacol. Biol. Psychiatry20063061155115810.1016/j.pnpbp.2006.03.036 16707201
    [Google Scholar]
  148. SanacoraG. RothmanD.L. MasonG. KrystalJ.H. Clinical studies implementing glutamate neurotransmission in mood disorders.Ann. N. Y. Acad. Sci.20031003129230810.1196/annals.1300.018 14684453
    [Google Scholar]
  149. HashimotoK. SawaA. IyoM. Increased levels of glutamate in brains from patients with mood disorders.Biol. Psychiatry200762111310131610.1016/j.biopsych.2007.03.017 17574216
    [Google Scholar]
  150. LowyM.T. GaultL. YamamotoB.K. Adrenalectomy attenuates stress-induced elevations in extracellular glutamate concentrations in the hippocampus.J. Neurochem.19936151957196010.1111/j.1471‑4159.1993.tb09839.x 7901339
    [Google Scholar]
  151. ReznikovL.R. GrilloC.A. PiroliG.G. PasumarthiR.K. ReaganL.P. FadelJ. Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: Differential effects of antidepressant treatment.Eur. J. Neurosci.200725103109311410.1111/j.1460‑9568.2007.05560.x 17561824
    [Google Scholar]
  152. BartanuszV. AubryJ.M. PagliusiS. JezovaD. BaffiJ. KissJ.Z. Stress-induced changes in messenger RNA levels of N-methyl-d-aspartate and AMPA receptor subunits in selected regions of the rat hippocampus and hypothalamus.Neuroscience199566224725210.1016/0306‑4522(95)00084‑V 7477869
    [Google Scholar]
  153. TrullasR. SkolnickP. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions.Eur. J. Pharmacol.1990185111010.1016/0014‑2999(90)90204‑J 2171955
    [Google Scholar]
  154. NewportD.J. CarpenterL.L. McDonaldW.M. PotashJ.B. TohenM. NemeroffC.B. Ketamine and other NMDA antagonists: Early clinical trials and possible mechanisms in depression.Am. J. Psychiatry20151721095096610.1176/appi.ajp.2015.15040465 26423481
    [Google Scholar]
  155. SchoeppD.D. Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.J. Pharmacol. Exp. Ther.200129911220 11561058
    [Google Scholar]
  156. FanM. RaymondL. N-Methyl-d-aspartate (NMDA) receptor function and excitotoxicity in Huntington’s disease.Prog. Neurobiol.2007815-627229310.1016/j.pneurobio.2006.11.003 17188796
    [Google Scholar]
  157. GielenM. RetchlessB.S. MonyL. JohnsonJ.W. PaolettiP. Mechanism of differential control of NMDA receptor activity by NR2 subunits.Nature2009459724770370710.1038/nature07993 19404260
    [Google Scholar]
  158. FurukawaH. SinghS.K. MancussoR. GouauxE. Subunit arrangement and function in NMDA receptors.Nature2005438706518519210.1038/nature04089 16281028
    [Google Scholar]
  159. YaoY. MayerM.L. Characterization of a soluble ligand binding domain of the NMDA receptor regulatory subunit NR3A.J. Neurosci.200626174559456610.1523/JNEUROSCI.0560‑06.2006 16641235
    [Google Scholar]
  160. HarrisonN.L. SimmondsM.A. Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex.Br. J. Pharmacol.198584238139110.1111/j.1476‑5381.1985.tb12922.x 2858237
    [Google Scholar]
  161. ChindoB.A. AdzuB. YahayaT.A. GamanielK.S. Ketamine-enhanced immobility in forced swim test: A possible animal model for the negative symptoms of schizophrenia.Prog. Neuropsychopharmacol. Biol. Psychiatry201238231031610.1016/j.pnpbp.2012.04.018 22561603
    [Google Scholar]
  162. MoghaddamB. AdamsB. VermaA. DalyD. Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.J. Neurosci.19971782921292710.1523/JNEUROSCI.17‑08‑02921.1997 9092613
    [Google Scholar]
  163. Jevtovic-TodorovicV. WozniakD.F. BenshoffN.D. OlneyJ.W. A comparative evaluation of the neurotoxic properties of ketamine and nitrous oxide.Brain Res.20018951-226426710.1016/S0006‑8993(01)02079‑0 11259788
    [Google Scholar]
  164. PriceR.B. NockM.K. CharneyD.S. MathewS.J. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression.Biol. Psychiatry200966552252610.1016/j.biopsych.2009.04.029 19545857
    [Google Scholar]
  165. GreenS.M. RothrockS.G. LynchE.L. Intramuscular ketamine for pediatric sedation in the emergency department: Safety profile in 1,022 cases.Ann. Emerg. Med.199831668869710.1016/S0196‑0644(98)70226‑4 9624307
    [Google Scholar]
  166. MathewS.J. ShahA. LapidusK. Ketamine for treatment-resistant unipolar depression: Current evidence.CNS Drugs201226318920410.2165/11599770‑000000000‑00000 22303887
    [Google Scholar]
  167. ParkM. NiciuM.J. ZarateC.A.Jr Novel glutamatergic treatments for severe mood disorders.Curr. Behav. Neurosci. Rep.20152419820810.1007/s40473‑015‑0050‑5 26824031
    [Google Scholar]
  168. SandersR.D. WeimannJ. MazeM. WarnerD.S. WarnerM.A. Biologic effects of nitrous oxide: A mechanistic and toxicologic review.Anesthesiology2008109470772210.1097/ALN.0b013e3181870a17 18813051
    [Google Scholar]
  169. WangM. YangY. DongZ. CaoJ. XuL. NR2B-containing N-methyl-D-aspartate subtype glutamate receptors regulate the acute stress effect on hippocampal long-term potentiation/long-term depression in vivo.Neuroreport200617121343134610.1097/01.wnr.0000227994.07799.6c 16951582
    [Google Scholar]
  170. MaengS. ZarateC.A.Jr DuJ. Cellular mechanisms underlying the antidepressant effects of ketamine: Role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors.Biol. Psychiatry200863434935210.1016/j.biopsych.2007.05.028 17643398
    [Google Scholar]
  171. PreskornS.H. BakerB. KolluriS. MennitiF.S. KramsM. LandenJ.W. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder.J. Clin. Psychopharmacol.200828663163710.1097/JCP.0b013e31818a6cea 19011431
    [Google Scholar]
  172. KempA.H. GordonE. RushA.J. WilliamsL.M. Improving the prediction of treatment response in depression: Integration of clinical, cognitive, psychophysiological, neuroimaging, and genetic measures.CNS Spectr.200813121066108610.1017/S1092852900017120 19179943
    [Google Scholar]
  173. LoD. GrossbergG.T. Use of memantine for the treatment of dementia.Expert Rev. Neurother.201111101359137010.1586/ern.11.132 21955192
    [Google Scholar]
  174. LenzeE.J. SkidmoreE.R. BegleyA.E. NewcomerJ.W. ButtersM.A. WhyteE.M. Memantine for late-life depression and apathy after a disabling medical event: A 12-week, double-blind placebo-controlled pilot study.Int. J. Geriatr. Psychiatry201227997498010.1002/gps.2813 22173933
    [Google Scholar]
  175. HuberT. DietrichD. EmrichH. Possible use of amantadine in depression.Pharmacopsychiatry1999322475510.1055/s‑2007‑979191 10333162
    [Google Scholar]
  176. FersztR. KühlK.P. BodeL. Amantadine revisited: an open trial of amantadinesulfate treatment in chronically depressed patients with Borna disease virus infection.Pharmacopsychiatry199932414214710.1055/s‑2007‑979220 10505484
    [Google Scholar]
  177. RogózZ. SkuzaG. DanielW.A. WójcikowskiJ. DudekD. WróbelA. Amantadine as an additive treatment in patients suffering from drug-resistant unipolar depression.Pharmacol. Rep.2007596778784 18195470
    [Google Scholar]
  178. SumiyoshiT. AnilA.E. JinD. JayathilakeK. LeeM. MeltzerH.Y. Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: Relation to negative symptoms.Int. J. Neuropsychopharmacol.2004711810.1017/S1461145703003900 14720317
    [Google Scholar]
  179. MoskalJ.R. BurchR. BurgdorfJ.S. GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists.Expert Opin. Investig. Drugs201423224325410.1517/13543784.2014.852536 24251380
    [Google Scholar]
  180. GoodchildC.S. GABA receptors and benzodiazepines.Br. J. Anaesth.199371112713310.1093/bja/71.1.127 8393687
    [Google Scholar]
  181. HaefelyW. Benzodiazepine interactions with GABA receptors.Neurosci. Lett.198447320120610.1016/0304‑3940(84)90514‑7 6147796
    [Google Scholar]
  182. IzquierdoI. PereiraM.E. MedinaJ.H. Benzodiazepine receptor ligand influences on acquisition: Suggestion of an endogenous modulatory mechanism mediated by benzodiazepine receptors.Behav. Neural Biol.1990541274110.1016/0163‑1047(90)91221‑V 1974134
    [Google Scholar]
  183. WesselmanJ.P.M. van WilgenburgH. LongS.K. The effects of pentobarbital and benzodiazepines on GABA-responses in the periphery and spinal cord in vitro.Neurosci. Lett.1991128226126410.1016/0304‑3940(91)90275‑X 1658694
    [Google Scholar]
  184. PotierM.C. Prado de CarvalhoL. DoddR.H. BesselievreR. RossierJ. In vivo binding of beta-carbolines in mice: Regional differences and correlation of occupancy to pharmacological effects.Mol. Pharmacol.1988342124128 2842651
    [Google Scholar]
  185. MellonS.H. GriffinL.D. Neurosteroids: Biochemistry and clinical significance.Trends Endocrinol. Metab.2002131354310.1016/S1043‑2760(01)00503‑3 11750861
    [Google Scholar]
  186. LambertJ.J. BelelliD. Hill-VenningC. CallachanH. PetersJ.A. Neurosteroid modulation of native and recombinant GABAA receptors.Cell. Mol. Neurobiol.199616215517410.1007/BF02088174 8743967
    [Google Scholar]
  187. SpivakC.E. Desensitization and noncompetitive blockade of GABAA receptors in ventral midbrain neurons by a neurosteroid dehydroepiandrosterone sulfate.Synapse199416211312210.1002/syn.890160205 7515198
    [Google Scholar]
  188. MonnetF.P. MahéV. RobelP. BaulieuE.E. Neurosteroids, via sigma receptors, modulate the [3H]norepinephrine release evoked by N-methyl-D-aspartate in the rat hippocampus.Proc. Natl. Acad. Sci.19959293774377810.1073/pnas.92.9.3774 7731982
    [Google Scholar]
  189. ZhuW.J. WangJ.F. KruegerK.E. ViciniS. δ subunit inhibits neurosteroid modulation of GABAA receptors.J. Neurosci.199616216648665610.1523/JNEUROSCI.16‑21‑06648.1996 8824305
    [Google Scholar]
  190. KostandyB.B. The role of glutamate in neuronal ischemic injury: The role of spark in fire.Neurol. Sci.201233222323710.1007/s10072‑011‑0828‑5 22044990
    [Google Scholar]
  191. MonyL. KewJ.N.C. GunthorpeM.J. PaolettiP. Allosteric modulators of NR2B-containing NMDA receptors: Molecular mechanisms and therapeutic potential.Br. J. Pharmacol.200915781301131710.1111/j.1476‑5381.2009.00304.x 19594762
    [Google Scholar]
  192. YuanH. LowC.M. MoodyO.A. JenkinsA. TraynelisS.F. Ionotropic GABA and glutamate receptor mutations and human neurologic diseases.Mol. Pharmacol.201588120321710.1124/mol.115.097998 25904555
    [Google Scholar]
  193. TraynelisS.F. WollmuthL.P. McBainC.J. Glutamate receptor ion channels: Structure, regulation, and function.Pharmacol. Rev.201062340549610.1124/pr.109.002451 20716669
    [Google Scholar]
  194. MiladinovicT. NashedM. SinghG. Overview of glutamatergic dysregulation in central pathologies.Biomolecules2015543112314110.3390/biom5043112 26569330
    [Google Scholar]
/content/journals/cprr/10.2174/0126660822262191231024081805
Loading
/content/journals/cprr/10.2174/0126660822262191231024081805
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test