Abstract
In the brain, the four subunits of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, glutamate A1 (GluA1), GluA2, GluA3, and GluA4 form functionally different tetramers. Of these, GluA1 is very important. It forms calcium-permeable (without GluA2) AMPA receptors and induces the trafficking and integration of AMPA receptors within synaptic membranes. Increased GluA1 expression and their phosphorylation are common mechanisms for the treatment of Alzheimer’s disease, schizophrenia, depression, and chronic drug addiction. Moreover, GluA1 is also involved in pain and epilepsy. Increased phosphorylation of serine831 in the GluA1 receptor is a mechanism necessary to alleviate Alzheimer’s disease and depression. GluA1-/- knockout mice are used as a model of schizophrenia. A decrease in the total cell AMPA receptor currents and phosphorylation of serine845 of GluA1 is observed in chronic drug addiction. Increased expression of GluA1 causes pain and is involved in epilepsy. GluA1-promoting AMPA receptor potentiators could be used to treat Alzheimer’s disease and memory loss. In conclusion, GluA1 agonists or antagonists might be effective in various disorders and conditions of the central nervous system that are based on GluA1 status at the synaptic region.
About the authors
Jingli Zhang, MD, PhD, he graduated from the Department of Medical Treatment (1980–1985), the Second Military Medical University in Shanghai; received his MSc in Neurobiology (1988–1991), and PhD in Neurology (1998–2001) from the Military Postgraduate Medical School in Beijing, PR China. He worked as a Residency Physician (1985–1988), Department of Neurology, Chinese People’s Liberation Army (PLA) 261 Hospital in Beijing; a Research Assistant Professor (1991–2004), Laboratory of Anti-aging Neurobiology, Institute of Geriatrics and Gerontology, PLA General Hospital, Beijing, PR China; a Postdoc Fellow (2004–2009), and a Research Associate (2009–2010) in the USA; a Senior Lecturer (2011–present) in the Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Malaysia.
Prof. Dr. Jafri Malin Abdullah MD (USM) holds the Certification of Specialization in Neurosurgery and a PhD from the University of Ghent, Belgium. He is a Fellow of the American College of Surgeons, the Royal College of Surgeons of Edinburgh and the Academy of Sciences, Malaysia. He is Professor of Neurosciences and the Director of the P3 Neuroscience Center. His research is focused on neurochemistry, neurogenetics, CNS tuberculosis, epilepsy, pain, functional MRI, magnetoencephalography, high density electroencephalography, patch clamp electrophysiology and neural stem cell culture. He has 145 publications in peer-reviewed journals and is the Editor of the Malaysian Journal of Medical Sciences and is on the editorial board member of six international neuroscience journals in Europe, USA, Australia, Japan, India and China. He has authored 8 textbooks and 12 textbook chapters, as well as graduated 35 neurosurgeons, a Neurologist, 10 Master of Science (Neurosciences), 3 PhDs and initiated Asia’s first Integrated Doctor of Neuroscience Program.
The work was supported by the Incentive Grant (October 2011–October 2012) and a Short Term Grant (304/PPSP/61312047, June 2012–June 2014) from the Universiti Sains Malaysia to Dr. Jingli Zhang and Prof. Dr. Jafri Malin Abdullah, et al.
References
Aitta-aho, T., Möykkynen, T.P., Panhelainen, A.E., Vekovischeva, O.Y., Bäckström, P., and Korpi, E.R. (2012). Importance of GluA1 subunit-containing AMPA glutamate receptors for morphine state-dependency. PLoS One 7, e38325.10.1371/journal.pone.0038325Search in Google Scholar PubMed PubMed Central
Bannerman, D.M. (2009). Fractionating spatial memory with glutamate receptor subunit-knockout mice. Biochem. Soc. Trans. 37, 1323–1327.10.1042/BST0371323Search in Google Scholar PubMed
Barbon, A., Caracciolo, L., Orlandi, C., Musazzi, L., Mallei, A., La Via, L., Bonini, D., Mora, C., Tardito, D., Gennarelli, M., et al. (2011). Chronic antidepressant treatments induce a time-dependent up-regulation of AMPA receptor subunit protein levels. Neurochem. Int. 59, 896–905.10.1016/j.neuint.2011.07.013Search in Google Scholar PubMed
Barkóczi, B., Juhász, G., Averkin, R.G., Vörös, I., Vertes, P., Penke, B., and Szegedi, V. (2012). GluA1 phosphorylation alters evoked firing pattern in vivo. Neural. Plast. 2012, 286215.10.1155/2012/286215Search in Google Scholar PubMed PubMed Central
Barkus, C., Feyder, M., Graybeal, C., Wright, T., Wiedholz, L., Izquierdo, A., Kiselycznyk, C., Schmitt, W., Sanderson, D.J., Rawlins, J.N., et al. (2012). Do GluA1 knockout mice exhibit behavioral abnormalities relevant to the negative or cognitive symptoms of schizophrenia and schizoaffective disorder? Neuropharmacology 62, 1263–1272.10.1016/j.neuropharm.2011.06.005Search in Google Scholar PubMed PubMed Central
Ben Abdallah, N.M., Fuss, J., Trusel, M., Galsworthy, M.J., Bobsin, K., Colacicco, G., Deacon, R.M., Riva, M.A., Kellendonk, C., Sprengel, R., et al. (2011). The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia. Exp. Neurol. 227, 42–52.10.1016/j.expneurol.2010.09.008Search in Google Scholar PubMed
Carlezon, W.A. Jr. and Thomas, M.J. (2009). Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis. Neuropharmacology 56, 122–132.10.1016/j.neuropharm.2008.06.075Search in Google Scholar PubMed PubMed Central
Chao, S.Z., Ariano, M.A., Peterson, D.A., and Wolf, M.E. (2002). D1 dopamine receptor stimulation increases GluR1 surface expression in nucleus accumbens neurons. J. Neurochem. 83, 704–712.10.1046/j.1471-4159.2002.01164.xSearch in Google Scholar PubMed
Erickson, M.A., Maramara, L.A., and Lisman, J. (2010). A single brief burst induces GluR1-dependent associative short-term potentiation: A potential mechanism for short-term memory. J. Cogn. Neurosci. 22, 2530–2540.10.1162/jocn.2009.21375Search in Google Scholar PubMed PubMed Central
Ferrario, C.R., Loweth, J.A., Milovanovic, M., Ford, K.A., Galiñanes, G.L., Heng, L.J., Tseng, K.Y., and Wolf, M.E. (2011). Alterations in AMPA receptor subunits and TARPs in the rat nucleus accumbens related to the formation of Ca²+-permeable AMPA receptors during the incubation of cocaine craving. Neuropharmacology 61, 1141–1151.10.1016/j.neuropharm.2011.01.021Search in Google Scholar PubMed PubMed Central
Fitzgerald, P.J., Barkus, C., Feyder, M., Wiedholz, L.M., Chen, Y.C., Karlsson, R.M., Machado-Vieira, R., Graybeal, C., Sharp, T., Zarate, C., et al. (2010). Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? Neurobiol. Dis. 40, 608–621.Search in Google Scholar
Frey, M.C., Sprengel, R., and Nevian, T. (2009). Activity pattern-dependent long-term potentiation in neocortex and hippocampus of GluA1 (GluR-A) subunit-deficient mice. J. Neurosci. 29, 5587–5596.10.1523/JNEUROSCI.5314-08.2009Search in Google Scholar PubMed PubMed Central
Frølund, S., Bella, A., Kristensen, A.S., Ziegler, H.L., Witt, M., Olsen, C.A., Strømgaard, K., Franzyk, H., and Jaroszewski, J.W. (2010). Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: discovery of nanomolar, nonselective, and use-dependent antagonists. J. Med. Chem. 53, 7441–7451.10.1021/jm100886hSearch in Google Scholar PubMed
Gómez-Soriano, J., Goiriena, E., and Taylor, J. (2010). Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury. Br. J. Pharmacol. 161, 972–975.10.1111/j.1476-5381.2010.00964.xSearch in Google Scholar PubMed PubMed Central
Hamad, M.I., Ma-Högemeier, Z.L., Riedel, C., Conrads, C., Veitinger, T., Habijan, T., Schulz, J.N., Krause, M., Wirth, M.J., Hollmann, M., et al. (2011). Cell class-specific regulation of neocortical dendrite and spine growth by AMPA receptor splice and editing variants. Development 138, 4301–4313.10.1242/dev.071076Search in Google Scholar PubMed
Harmel, N., Cokic, B., Zolles, G., Berkefeld, H., Mauric, V., Fakler, B., Stein, V., and Klöcker, N. (2012). AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling. PLoS One 7, e30681.10.1371/journal.pone.0030681Search in Google Scholar PubMed PubMed Central
He, K., Lee, A., Song, L., Kanold, P.O., and Lee, H.K. (2011). AMPA receptor subunit GluR1 (GluA1) serine-845 site is involved in synaptic depression but not in spine shrinkage associated with chemical long-term depression. J. Neurophysiol. 105, 1897–1907.10.1152/jn.00913.2010Search in Google Scholar PubMed PubMed Central
Hendriksen, H., Bink, D.I., Daniels, E.G., Pandit, R., Piriou, C., Slieker, R., Westphal, K.G., Olivier, B., and Oosting, R.S. (2012). Re-exposure and environmental enrichment reveal NPY-Y1 as a possible target for post-traumatic stress disorder. Neuropharmacology 63, 733–742.10.1016/j.neuropharm.2012.05.028Search in Google Scholar PubMed
Kennard, J.T., Barmanray, R., Sampurno, S., Ozturk, E., Reid, C.A., Paradiso, L., D’Abaco, G.M., Kaye, A.H., Foote, S.J., O’Brien, T.J., et al. (2011). Stargazin and AMPA receptor membrane expression is increased in the somatosensory cortex of Genetic Absence Epilepsy Rats from Strasbourg. Neurobiol. Dis. 42, 48–54.10.1016/j.nbd.2011.01.003Search in Google Scholar PubMed
Lane, D.A., Reed, B., Kreek, M.J., and Pickel, V.M. (2011). Differential glutamate AMPA-receptor plasticity in subpopulations of VTA neurons in the presence or absence of residual cocaine: implications for the development of addiction. Neuropharmacology 61, 1129–1140.10.1016/j.neuropharm.2010.12.031Search in Google Scholar PubMed PubMed Central
Lee, H.K., Takamiya, K., He, K., Song, L., and Huganir, R.L. (2010). Specific roles of AMPA receptor subunit GluR1 (GluA1) phosphorylation sites in regulating synaptic plasticity in the CA1 region of hippocampus. J. Neurophysiol. 103, 479–489.10.1152/jn.00835.2009Search in Google Scholar PubMed PubMed Central
Liu, S., Zheng, D., Peng, X.X., Cabeza de Vaca, S., and Carr, K.D. (2011). Enhanced cocaine-conditioned place preference and associated brain regional levels of BDNF, p-ERK1/2 and p-Ser845-GluA1 in food-restricted rats. Brain Res. 1400, 31–41.10.1016/j.brainres.2011.05.028Search in Google Scholar PubMed PubMed Central
Miñano-Molina, A.J., España, J., Martín, E., Barneda-Zahonero, B., Fadó, R., Solé, M., Trullás, R., Saura, C.A., and Rodríguez-Alvarez, J. (2011). Soluble oligomers of amyloid-β peptide disrupt membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction. J. Biol. Chem. 286, 27311–27321.10.1074/jbc.M111.227504Search in Google Scholar PubMed PubMed Central
Montgomery, K.E., Kessler, M., and Arai, A.C. (2009). Modulation of agonist binding to AMPA receptors by 1-(1,4-benzodioxan-6-ylcarbonyl)piperidine (CX546): differential effects across brain regions and GluA1-4/transmembrane AMPA receptor regulatory protein combinations. J. Pharmacol. Exp. Ther. 331, 965–974.10.1124/jpet.109.158014Search in Google Scholar PubMed PubMed Central
Moriguchi, S. (2011). Pharmacological study on Alzheimer’s drugs targeting calcium/calmodulin-dependent protein kinase II. J. Pharmacol. Sci. 117, 6–11.10.1254/jphs.11R06CPSearch in Google Scholar PubMed
Murray, T.K., Whalley, K., Robinson, C.S., Ward, M.A., Hicks, C.A., Lodge, D., Vandergriff, J.L., Baumbarger, P., Siuda, E., Gates, M., et al. (2003). LY503430, a novel α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor potentiator with functional, neuroprotective and neurotrophic effects in rodent models of Parkinson’s disease. J. Pharmacol. Exp. Ther. 306, 752–762.10.1124/jpet.103.049445Search in Google Scholar PubMed
Ninomiya, M., Numakawa, T., Adachi, N., Furuta, M., Chiba, S., Richards, M., Shibata, S., and Kunugi, H. (2010). Cortical neurons from intrauterine growth retardation rats exhibit lower response to neurotrophin BDNF. Neurosci. Lett. 476, 104–109.10.1016/j.neulet.2010.03.082Search in Google Scholar PubMed
O’Brien, R.J. and Wong, P.C. (2011). Amyloid precursor protein processing and Alzheimer’s disease. Annu. Rev. Neurosci. 34, 185–204.10.1146/annurev-neuro-061010-113613Search in Google Scholar PubMed PubMed Central
Pritchard, S.M., Dolan, P.J., Vitkus, A., and Johnson, G.V. (2011). The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics. J. Cell Mol. Med. 15, 1621–1635.10.1111/j.1582-4934.2011.01273.xSearch in Google Scholar PubMed PubMed Central
Procaccini, C., Aitta-aho, T., Jaako-Movits, K., Zharkovsky, A., Panhelainen, A., Sprengel, R., Linden, A.M., and Korpi, E.R. (2011). Excessive novelty-induced c-Fos expression and altered neurogenesis in the hippocampus of GluA1 knockout mice. Eur. J. Neurosci. 33, 161–174.10.1111/j.1460-9568.2010.07485.xSearch in Google Scholar PubMed
Qi, H., Mailliet, F., Spedding, M., Rocher, C., Zhang, X., Delagrange, P., McEwen, B., Jay, T.M., and Svenningsson, P. (2009). Antidepressants reverse the attenuation of the neurotrophic MEK/MAPK cascade in frontal cortex by elevated platform stress; reversal of effects on LTP is associated with GluA1 phosphorylation. Neuropharmacology 56, 37–46.10.1016/j.neuropharm.2008.06.068Search in Google Scholar PubMed
Reimers, J.M., Milovanovic, M., and Wolf, M.E. (2011). Quantitative analysis of AMPA receptor subunit composition in addiction-related brain regions. Brain Res. 1367, 223–233.10.1016/j.brainres.2010.10.016Search in Google Scholar PubMed PubMed Central
Romberg, C., Raffel, J., Martin, L., Sprengel, R., Seeburg, P.H., Rawlins, J.N., Bannerman, D.M., and Paulsen, O. (2009). Induction and expression of GluA1 (GluR-A)-independent LTP in the hippocampus. Eur. J. Neurosci. 29, 1141–1152.10.1111/j.1460-9568.2009.06677.xSearch in Google Scholar PubMed PubMed Central
Sanderson, D.J. and Bannerman, D.M. (2012). The role of habituation in hippocampus-dependent spatial working memory tasks: evidence from GluA1 AMPA receptor subunit knockout mice. Hippocampus 22, 981–994.10.1002/hipo.20896Search in Google Scholar PubMed PubMed Central
Sanderson, D.J., Good, M.A., Skelton, K., Sprengel, R., Seeburg, P.H., Rawlins, J.N., and Bannerman, D.M. (2009). Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model. Learn. Mem. 16, 379–386.10.1101/lm.1339109Search in Google Scholar PubMed PubMed Central
Sanderson, D.J., McHugh, S.B., Good, M.A., Sprengel, R., Seeburg, P.H., Rawlins, J.N., and Bannerman, D.M. (2010). Spatial working memory deficits in GluA1 AMPA receptor subunit knockout mice reflect impaired short-term habituation: evidence for Wagner’s dual-process memory model. Neuropsychologia 48, 2303–2315.10.1016/j.neuropsychologia.2010.03.018Search in Google Scholar PubMed PubMed Central
Sanderson, D.J., Sprengel, R., Seeburg, P.H., and Bannerman, D.M. (2011). Deletion of the GluA1 AMPA receptor subunit alters the expression of short-term memory. Learn. Mem. 18, 128–131.10.1101/lm.2014911Search in Google Scholar PubMed PubMed Central
Shevtsova, O. and Leitch, B. (2012). Selective loss of AMPA receptor subunits at inhibitory neuron synapses in the cerebellum of the ataxic stargazer mouse. Brain Res. 1427, 54–64.10.1016/j.brainres.2011.10.022Search in Google Scholar PubMed
Steele, D., Moore, R.L., Swan, N.A., Grant, J.S., and Keltner, N.L. (2012). Biological perspectives: the role of glutamate in schizophrenia and its treatment. Perspect. Psychiatr. Care 48, 125–128.10.1111/j.1744-6163.2012.00333.xSearch in Google Scholar PubMed
Sun, X., Zhao, Y., and Wolf, M.E. (2005). Dopamine receptor stimulation modulates AMPA receptor synaptic insertion in prefrontal cortex neurons. J. Neurosci. 25, 7342–7351.10.1523/JNEUROSCI.4603-04.2005Search in Google Scholar PubMed PubMed Central
Taylor, A.M., Niewoehner, B., Seeburg, P.H., Sprengel, R., Rawlins, J.N., Bannerman, D.M., and Sanderson, D.J. (2011). Dissociations within short-term memory in GluA1 AMPA receptor subunit knockout mice. Behav. Brain Res. 224, 8–14.10.1016/j.bbr.2011.05.016Search in Google Scholar PubMed PubMed Central
Toyoda, H., Zhao, M.G., Ulzhöfer, B., Wu, L.J., Xu, H., Seeburg, P.H., Sprengel, R., Kuner, R., and Zhuo, M. (2009). Roles of the AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulate cortex. Mol. Pain 5, 46.10.1186/1744-8069-5-46Search in Google Scholar PubMed PubMed Central
Tropea, T.F., Kabir, Z.D., Kaur, G., Rajadhyaksha, A.M., and Kosofsky, B.E. (2011). Enhanced dopamine D1 and BDNF signaling in the adult dorsal striatum but not nucleus accumbens of prenatal cocaine treated mice. Front. Psychiatry 2, 67.10.3389/fpsyt.2011.00067Search in Google Scholar PubMed PubMed Central
Ward, S.E., Bax, B.D., and Harries, M. (2010). Challenges for and current status of research into positive modulators of AMPA receptors. Br. J. Pharmacol. 160, 181–190.10.1111/j.1476-5381.2010.00726.xSearch in Google Scholar PubMed PubMed Central
Wright, A. and Vissel, B. (2012). The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain. Front. Mol. Neurosci. 5, 34.10.3389/fnmol.2012.00034Search in Google Scholar PubMed PubMed Central
Xia, Y., Portugal, G.S., Fakira, A.K., Melyan, Z., Neve, R., Lee, H.T., Russo, S.J., Liu, J., and Morón, J.A. (2011). Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine. J. Neurosci. 31, 16279–16291.10.1523/JNEUROSCI.3835-11.2011Search in Google Scholar PubMed PubMed Central
Yao, G., Zong, Y., Gu, S., Zhou, J., Xu, H., Mathews, I.I., and Jin, R. (2011). Crystal structure of the glutamate receptor GluA1 N-terminal domain. Biochem. J. 438, 255–263.10.1042/BJ20110801Search in Google Scholar PubMed PubMed Central
Yamamoto, D.J. and Zahniser, N.R. (2012). Differences in rat dorsal striatal NMDA and AMPA receptors following acute and repeated cocaine-induced locomotor activation. PLoS One 7, e37673.10.1371/journal.pone.0037673Search in Google Scholar PubMed PubMed Central
Zhang, X., Lee, T.H., Davidson, C., Lazarus, C., Wetsel, W.C., and Ellinwood, E.H. (2007). Reversal of cocaine-induced behavioral sensitization and associated phosphorylation of the NR2B and GluR1 subunits of the NMDA and AMPA receptors. Neuropsychopharmacology 32, 377–387.10.1038/sj.npp.1301101Search in Google Scholar PubMed
©2013 by Walter de Gruyter Berlin Boston
