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Intercellular Glutamate Signaling in the Nervous System and Beyond

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Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607
Cite this: ACS Chem. Neurosci. 2010, 1, 1, 4–12
Publication Date (Web):October 9, 2009
Copyright © 2009 American Chemical Society

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    Most intercellular glutamate signaling in the nervous system occurs at synapses. Some intercellular glutamate signaling occurs outside synapses, however, and even outside the nervous system where high ambient extracellular glutamate might be expected to preclude the effectiveness of glutamate as an intercellular signal. Here, I briefly review the types of intercellular glutamate signaling in the nervous system and beyond, with emphasis on the diversity of signaling mechanisms and fundamental unanswered questions.

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    22. Martín A. Toderi, Dzmitry Vaido, Dolores Bozovic, , , , . Optical techniques for imaging activity in fibers innervating saccular hair cells. 2022, 38.
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    55. Carlos A Gutierrez, Mary M Staehle. A control system analysis of the dynamic response of N-methyl-D-aspartate glutamate receptors to alcoholism and alcohol withdrawal. Theoretical Biology and Medical Modelling 2015, 12 (1)
    56. Rıfat Emrah Özel, Akhtar Hayat, Silvana Andreescu. Recent Developments in Electrochemical Sensors for the Detection of Neurotransmitters for Applications in Biomedicine. Analytical Letters 2015, 48 (7) , 1044-1069.
    57. Yuyu Wang, Dazhi Wang, Lin Lin, Minghua Wang. Quantitative proteomic analysis reveals proteins involved in the neurotoxicity of marine medaka Oryzias melastigma chronically exposed to inorganic mercury. Chemosphere 2015, 119 , 1126-1133.
    58. Masashi Nakahama, Julien Reboul, Kenji Yoshida, Shuhei Furukawa, Susumu Kitagawa. l -Glutamic acid release from a series of aluminum-based isoreticular porous coordination polymers. Journal of Materials Chemistry B 2015, 3 (20) , 4205-4212.
    59. Shu Feng, Zhaofa Xu, Wei Liu, Yuehui Li, Yu Deng, Bin Xu. Preventive Effects of Dextromethorphan on Methylmercury-Induced Glutamate Dyshomeostasis and Oxidative Damage in Rat Cerebral Cortex. Biological Trace Element Research 2014, 159 (1-3) , 332-345.
    60. David N. Guilfoyle, Scott Gerum, Csaba Vadasz. In vivo Proton NMR Spectroscopy of Genetic Mouse Models BALB/cJ and C57BL/6By: Variation in Hippocampal Glutamate Level and the Metabotropic Glutamate Receptor, Subtype 7 (Grm7) Gene. Journal of Molecular Neuroscience 2014, 53 (1) , 135-141.
    61. R. Pérez-Rodríguez, A.M. Oliván, C. Roncero, J. Morón-Oset, M.P. González, M.J. Oset-Gasque. Glutamate triggers neurosecretion and apoptosis in bovine chromaffin cells through a mechanism involving NO production by neuronal NO synthase activation. Free Radical Biology and Medicine 2014, 69 , 390-402.
    62. Brian G. Forde. Glutamate signalling in roots. Journal of Experimental Botany 2014, 65 (3) , 779-787.
    63. J.J. Xu, P. Diaz, B. Bie, F. Astruc-Diaz, J. Wu, H. Yang, D.L. Brown, M. Naguib. Spinal gene expression profiling and pathways analysis of a CB2 agonist (MDA7)-targeted prevention of paclitaxel-induced neuropathy. Neuroscience 2014, 260 , 185-194.
    64. Pablo R. Brumovsky. VGLUTs in Peripheral Neurons and the Spinal Cord: Time for a Review. ISRN Neurology 2013, 2013 , 1-28.
    65. Wei Liu, Zhaofa Xu, Yu Deng, Bin Xu, Yangang Wei, Tianyao Yang. Protective Effects of Memantine Against Methylmercury-Induced Glutamate Dyshomeostasis and Oxidative Stress in Rat Cerebral Cortex. Neurotoxicity Research 2013, 24 (3) , 320-337.
    66. M. Malet, C.A. Vieytes, K.H. Lundgren, R.P. Seal, E. Tomasella, K.B. Seroogy, T. Hökfelt, G.F. Gebhart, P.R. Brumovsky. Transcript expression of vesicular glutamate transporters in lumbar dorsal root ganglia and the spinal cord of mice – Effects of peripheral axotomy or hindpaw inflammation. Neuroscience 2013, 248 , 95-111.
    67. Fabiana K. Ludka, Andréa D.E. Zomkowski, Mauricio P. Cunha, Tharine Dal-Cim, Ana Lúcia B. Zeni, Ana Lúcia S. Rodrigues, Carla I. Tasca. Acute atorvastatin treatment exerts antidepressant-like effect in mice via the l-arginine–nitric oxide–cyclic guanosine monophosphate pathway and increases BDNF levels. European Neuropsychopharmacology 2013, 23 (5) , 400-412.
    68. Anurag Mishra, Sven Gottschalk, Jörn Engelmann, David Parker. Responsive imaging probes for metabotropic glutamate receptors. Chem. Sci. 2012, 3 (1) , 131-135.
    69. Chandni A. Vyas, Scott M. Rawls, Robert B. Raffa, Jonathan G. Shackman. Glutamate and aspartate measurements in individual planaria by rapid capillary electrophoresis. Journal of Pharmacological and Toxicological Methods 2011, 63 (1) , 119-122.

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