DOI QR코드

DOI QR Code

Fragile X Mental Retardation Protein in Learning-Related Synaptic Plasticity

  • Mercaldo, Valentina (Department of Physiology, Faculty of Medicine, University of Toronto) ;
  • Descalzi, Giannina (Department of Physiology, Faculty of Medicine, University of Toronto) ;
  • Zhuo, Min (Department of Physiology, Faculty of Medicine, University of Toronto)
  • Received : 2009.12.07
  • Accepted : 2009.12.09
  • Published : 2009.12.31

Abstract

Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP) due to silencing of the Fmr1 gene. As an RNA binding protein, FMRP is thought to contribute to synaptic plasticity by regulating plasticity-related protein synthesis and other signaling pathways. Previous studies have mostly focused on the roles of FMRP within the hippocampus - a key structure for spatial memory. However, recent studies indicate that FMRP may have a more general contribution to brain functions, including synaptic plasticity and modulation within the prefrontal cortex. In this brief review, we will focus on recent studies reported in the prefrontal cortex, including the anterior cingulate cortex (ACC). We hypothesize that alterations in ACC-related plasticity and synaptic modulation may contribute to various forms of cognitive deficits associated with FXS.

Keywords

Acknowledgement

Supported by : Canada Research Chair, Seoul National University

References

  1. Antar, L.N., Afroz, R., Dictenberg, J.B., Carroll, R.C., and Bassell, G.J. (2004). Metabotropic glutamate receptor activation regulates fragile x mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses. J. Neurosci. 24, 2648-2655 https://doi.org/10.1523/JNEUROSCI.0099-04.2004
  2. Bagni, C., and Greenough, W.T. (2005). From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome. Nat. Rev. Neurosci. 6, 376-387 https://doi.org/10.1038/nrn1667
  3. Bakker, C.E., Verheij, C., Willemsen, R., Vanderhelm, R., Oerlemans, F., Vermey, M., Bygrave, A., Hoogeveen, A.T., Oostra, B.A., and Reyniers, E. (1994). Fmr1 knockout mice: a model to study fragile X mental retardation. Cell 78, 23-33
  4. Bassell, G.J., and Gross, C. (2008). Reducing glutamate signaling pays off in fragile X. Nat. Med. 14, 249-250 https://doi.org/10.1038/nm0308-249
  5. Bassell, G.J., and Warren, S.T. (2008). Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 60, 201-214 https://doi.org/10.1016/j.neuron.2008.10.004
  6. Bear, M.F. (1996). A synaptic basis for memory storage in the cerebral cortex. Proc. Natl. Acad. Sci. USA 93, 13453-13459 https://doi.org/10.1073/pnas.93.24.13453
  7. Bear, M.F., Huber, K.M., and Warren, S.T. (2004). The mGluR theory of fragile X mental retardation. Trends Neurosci. 27, 370-377 https://doi.org/10.1016/j.tins.2004.04.009
  8. Bliss, T.V., and Collingridge, G.L. (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31-39 https://doi.org/10.1038/361031a0
  9. Bureau, I., Shepherd, G.M., and Svoboda, K. (2008). Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice. J. Neurosci. 28, 5178-5188 https://doi.org/10.1523/JNEUROSCI.1076-08.2008
  10. Castren, M., Lampinen, K.E., Miettinen, R., Koponen, E., Sipola, I., Bakker, C.E., Oostra, B.A., and Castren, E. (2002). BDNF regulates the expression of fragile X mental retardation protein mRNA in the hippocampus. Neurobiol. Dis. 11, 221-229 https://doi.org/10.1006/nbdi.2002.0544
  11. Centonze, D., Rossi, S., Mercaldo, V., Napoli, I., Ciotti, M.T., Chiara, V.D., Musella, A., Prosperetti, C., Calabresi, P., Bernardi, G., et al. (2007). Abnormal striatal GABA transmission in the mouse model for the fragile X syndrome. Biol. Psychiatry 63, 963-973
  12. Chen, L., and Toth, M. (2001). Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience 103, 1043-1050 https://doi.org/10.1016/S0306-4522(01)00036-7
  13. Collingridge, G.L., Isaac, J.T., and Wang, Y.T. (2004). Receptor trafficking and synaptic plasticity. Nat. Rev. Neurosci. 5, 952-962 https://doi.org/10.1038/nrn1556
  14. Comery, T.A., Harris, J.B., Willems, P.J., Oostra, B.A., Irwin, S.A., Weiler, I.J., and Greenough, W.T. (1997). Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc. Natl. Acad. Sci. USA 94, 5401-5404 https://doi.org/10.1073/pnas.94.10.5401
  15. Curia, G., Papouin, T., Seguela, P., and Avoli, M. (2009). Downregulation of tonic GABAergic inhibition in a mouse model of fragile X syndrome. Cereb. Cortex 19, 1515-1520 https://doi.org/10.1093/cercor/bhn159
  16. D'Antuono, M., Merlo, D., and Avoli, M. (2003). Involvement of cholinergic and gabaergic systems in the fragile X knockout mice. Neuroscience 119, 9-13 https://doi.org/10.1016/S0306-4522(03)00103-9
  17. D'Hulst, C., and Kooy, R.F. (2007). The GABAA receptor: a novel target for treatment of fragile X? Trends Neurosci. 30, 425-431 https://doi.org/10.1016/j.tins.2007.06.003
  18. D'Hulst, C., De Geest, N., Reeve, S.P., Van Dam, D., De Deyn, P.P., Hassan, B.A., and Kooy, R.F. (2006). Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res. 1121, 238-245 https://doi.org/10.1016/j.brainres.2006.08.115
  19. Desai, N.S., Casimiro, T.M., Gruber, S.M., and Vanderklish, P.W. (2006). Early postnatal plasticity in neocortex of Fmr1 knockout mice. J. Neurophysiol. 96, 1734-1745 https://doi.org/10.1152/jn.00221.2006
  20. Devys, D., Lutz, Y., Rouyer, N., Bellocq, J.P., and Mandel, J.L. (1993). The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat. Genet. 4, 335-340 https://doi.org/10.1038/ng0893-335
  21. Dobkin, C., Rabe, A., Dumas, R., El Idrissi, A., Haubenstock, H., and Brown, W.T. (2000). Fmr1 knockout mouse has a distinctive strain-specific learning impairment. Neuroscience 100, 423-429 https://doi.org/10.1016/S0306-4522(00)00292-X
  22. Dolen, G., Osterweil, E., Rao, B.S., Smith, G.B., Auerbach, B.D., Chattarji, S., and Bear, M.F. (2007). Correction of fragile X syndrome in mice. Neuron 56, 955-962 https://doi.org/10.1016/j.neuron.2007.12.001
  23. El Idrissi, A., Ding, X.H., Scalia, J., Trenkner, E., Brown, W.T., and Dobkin, C. (2005). Decreased GABA(A) receptor expression in the seizure-prone fragile X mouse. Neurosci. Lett. 377, 141-146 https://doi.org/10.1016/j.neulet.2004.11.087
  24. Feng, Y., Gutekunst, C.A., Eberhart, D.E., Yi, H., Warren, S.T., and Hersch, S.M. (1997). Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J. Neurosci. 17, 1539-1547
  25. Ferrari, F., Mercaldo, V., Piccoli, G., Sala, C., Cannata, S., Achsel, T., and Bagni, C. (2007). The fragile X mental retardation protein- RNP granules show an mGluR-dependent localization in the post-synaptic spines. Mol. Cell. Neurosci. 34, 343-354 https://doi.org/10.1016/j.mcn.2006.11.015
  26. Frankland, P.W., Wang, Y., Rosner, B., Shimizu, T., Balleine, B.W., Dykens, E.M., Ornitz, E.M., and Silva, A.J. (2004). Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice. Mol. Psychiatry 9, 417-425 https://doi.org/10.1038/sj.mp.4001432
  27. Galvez, R., and Greenough, W.T. (2005). Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome. Am. J. Med. Genet. A 135, 155-160
  28. Godfraind, J.M., Reyniers, E., De Boulle, K., D'Hooge, R., De Deyn, P.P., Bakker, C.E., Oostra, B.A., Kooy, R.F., and Willems, P.J. (1996). Long-term potentiation in the hippocampus of fragile X knockout mice. Am. J. Med. Genet. 64, 246-251 https://doi.org/10.1002/(SICI)1096-8628(19960809)64:2<246::AID-AJMG2>3.0.CO;2-S
  29. Gruss, M., and Braun, K. (2004). Age- and region-specific imbalances of basal amino acids and monoamine metabolism in limbic regions of female Fmr1 knock-out mice. Neurochem. Int. 45, 81-88 https://doi.org/10.1016/j.neuint.2003.12.001
  30. Hagerman, B. (2002). Speech recognition threshold in slightly and fully modulated noise for hearing-impaired subjects. Int. J. Audiol. 41, 321-329 https://doi.org/10.3109/14992020209090406
  31. Hagerman, P.J. (2008). The fragile X prevalence paradox. J. Med. Genet. 45, 498-499 https://doi.org/10.1136/jmg.2008.059055
  32. Hagerman, R.J., Berry-Kravis, E., Kaufmann, W.E., Ono, M.Y., Tartaglia, N., Lachiewicz, A., Kronk, R., Delahunty, C., Hessl, D., Visootsak, J., et al. (2009). Advances in the treatment of fragile X syndrome. Pediatrics 123, 378-390 https://doi.org/10.1542/peds.2008-0317
  33. Hou, L., Antion, M.D., Hu, D., Spencer, C.M., Paylor, R., and Klann, E. (2006). Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 51, 441-454 https://doi.org/10.1016/j.neuron.2006.07.005
  34. Hu, H., Qin, Y., Bochorishvili, G., Zhu, Y., van Aelst, L., and Zhu, J.J. (2008). Ras signaling mechanisms underlying impaired GluR1- dependent plasticity associated with fragile X syndrome. J. Neurosci. 28, 7847-7862 https://doi.org/10.1523/JNEUROSCI.1496-08.2008
  35. Huang, Y.Y., and Kandel, E.R. (1995). D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. Proc. Natl. Acad. Sci. USA 92, 2446-2450 https://doi.org/10.1073/pnas.92.7.2446
  36. Huber, K.M., Gallagher, S.M., Warren, S.T., and Bear, M.F. (2002). Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc. Natl. Acad. Sci. USA 99, 7746-7750 https://doi.org/10.1073/pnas.122205699
  37. Igartua, I., Solis, J.M., and Bustamante, J. (2007). Glycine-induced long-term synaptic potentiation is mediated by the glycine transporter GLYT1. Neuropharmacology 52, 1586-1595 https://doi.org/10.1016/j.neuropharm.2007.03.003
  38. Irwin, S.A., Idupulapati, M., Gilbert, M.E., Harris, J.B., Chakravarti, A.B., Rogers, E.J., Crisostomo, R.A., Larsen, B.P., Mehta, A., Alcantara, C.J., et al. (2002). Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am. J. Med. Genet. 111, 140-146 https://doi.org/10.1002/ajmg.10500
  39. Kandel, E.R. (2001). The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030- 1038 https://doi.org/10.1126/science.1067020
  40. Klann, E., and Dever, T.E. (2004). Biochemical mechanisms for translational regulation in synaptic plasticity. Nat. Rev. Neurosci. 5, 931-942 https://doi.org/10.1038/nrn1557
  41. Larson, J., Jessen, R.E., Kim, D., Fine, A.K., and du Hoffmann, J. (2005). Age-dependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein. J. Neurosci. 25, 9460-9469 https://doi.org/10.1523/JNEUROSCI.2638-05.2005
  42. Lauterborn, J.C., Rex, C.S., Kramar, E., Chen, L.Y., Pandyarajan, V., Lynch, G., and Gall, C.M. (2007). Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile X syndrome. J. Neurosci. 27, 10685-10694 https://doi.org/10.1523/JNEUROSCI.2624-07.2007
  43. Li, J., Pelletier, M.R., Perez Velazquez, J.L., and Carlen, P.L. (2002). Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Mol. Cell. Neurosci. 19, 138-151 https://doi.org/10.1006/mcne.2001.1085
  44. McBride, S.M., Choi, C.H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., Sehgal, A., Siwicki, K.K., Dockendorff, T.C., Nguyen, H.T., et al. (2005). Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45, 753-764 https://doi.org/10.1016/j.neuron.2005.01.038
  45. Menon, V., Leroux, J., White, C.D., and Reiss, A.L. (2004). Frontostriatal deficits in fragile X syndrome: relation to FMR1 gene expression. Proc. Natl. Acad. Sci. USA 101, 3615-3620 https://doi.org/10.1073/pnas.0304544101
  46. Meredith, R.M., Holmgren, C.D., Weidum, M., Burnashev, N., and Mansvelder, H.D. (2007). Increased threshold for spike-timingdependent plasticity is caused by unreliable calcium signaling in mice lacking fragile X gene FMR1. Neuron 54, 627-638 https://doi.org/10.1016/j.neuron.2007.04.028
  47. Mineur, Y.S., Sluyter, F., de Wit, S., Oostra, B.A., and Crusio, W.E. (2002). Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse. Hippocampus 12, 39-46 https://doi.org/10.1002/hipo.10005
  48. Missale, C., Nash, S.R., Robinson, S.W., Jaber, M., and Caron, M.G. (1998). Dopamine receptors: from structure to function. Physiol. Rev. 78, 189-225 https://doi.org/10.1152/physrev.1998.78.1.189
  49. Musumeci, S.A., Calabrese, G., Bonaccorso, C.M., D'Antoni, S., Brouwer, J.R., Bakker, C.E., Elia, M., Ferri, R., Nelson, D.L., Oostra, B.A., et al. (2007). Audiogenic seizure susceptibility is reduced in fragile X knockout mice after introduction of FMR1 transgenes. Exp. Neurol. 203, 233-240 https://doi.org/10.1016/j.expneurol.2006.08.007
  50. Nakamoto, M., Nalavadi, V., Epstein, M.P., Narayanan, U., Bassell, G.J., and Warren, S.T. (2007). Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc. Natl. Acad. Sci. USA 104, 15537-15542 https://doi.org/10.1073/pnas.0707484104
  51. Napoli, I., Mercaldo, V., Boyl, P.P., Eleuteri, B., Zalfa, F., De Rubeis, S., Di Marino, D., Mohr, E., Massimi, M., Falconi, M., et al. (2008). The fragile X syndrome protein represses activitydependent translation through CYFIP1, a new 4E-BP. Cell 134, 1042-1054 https://doi.org/10.1016/j.cell.2008.07.031
  52. Nicoll, R.A., and Malenka, R.C. (1995). Contrasting properties of two forms of long-term potentiation in the hippocampus. Nature 377, 115-118 https://doi.org/10.1038/377115a0
  53. Nimchinsky, E.A., Oberlander, A.M., and Svoboda, K. (2001). Abnormal development of dendritic spines in FMR1 knock-out mice. J. Neurosci. 21, 5139-5146
  54. Pacey, L.K., and Doering, L.C. (2007). Developmental expression of FMRP in the astrocyte lineage: implications for fragile X syndrome. Glia 55, 1601-1609 https://doi.org/10.1002/glia.20573
  55. Paradee, W., Melikian, H.E., Rasmussen, D.L., Kenneson, A., Conn, P.J., and Warren, S.T. (1999). Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function. Neuroscience 94, 185-192 https://doi.org/10.1016/S0306-4522(99)00285-7
  56. Price, T.J., Rashid, M.H., Millecamps, M., Sanoja, R., Entrena, J.M., and Cervero, F. (2007). Decreased nociceptive sensitization in mice lacking the fragile X mental retardation protein: role of mGluR1/5 and mTOR. J. Neurosci. 27, 13958-13967 https://doi.org/10.1523/JNEUROSCI.4383-07.2007
  57. Qiu, L.F., Hao, Y.H., Li, Q.Z., and Xiong, Z.Q. (2008). Fragile X syndrome and epilepsy. Neurosci. Bull. 24, 338-344 https://doi.org/10.1007/s12264-008-1221-0
  58. Reiss, A.L., and Dant, C.C. (2003). The behavioral neurogenetics of fragile X syndrome: analyzing gene-brain-behavior relationships in child developmental psychopathologies. Dev. Psychopathol. 15, 927-968
  59. Restivo, L., Ferrari, F., Passino, E., Sgobio, C., Bock, J., Oostra, B.A., Bagni, C., and Ammassari-Teule, M. (2005). Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome. Proc. Natl. Acad. Sci. USA 102, 11557-11562 https://doi.org/10.1073/pnas.0504984102
  60. Ronesi, J.A., and Huber, K.M. (2008). Metabotropic glutamate receptors and fragile x mental retardation protein: partners in translational regulation at the synapse. Sci. Signal. 1, pe6
  61. Sawaguchi, T., and Goldman-Rakic, P.S. (1991). D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 251, 947-950 https://doi.org/10.1126/science.1825731
  62. Shang, Y., Wang, H., Mercaldo, V., Li, X., Chen, T., and Zhuo, M. (2009). Fragile X mental retardation protein is required for chemically-induced long-term potentiation of the hippocampus in adult mice. J. Neurochem. 111, 635-646 https://doi.org/10.1111/j.1471-4159.2009.06314.x
  63. Tassone, F., Hagerman, R.J., Ikle, D.N., Dyer, P.N., Lampe, M., Willemsen, R., Oostra, B.A., and Taylor, A.K. (1999). FMRP expression as a potential prognostic indicator in fragile X syndrome. Am. J. Med. Genet. 84, 250-261 https://doi.org/10.1002/(SICI)1096-8628(19990528)84:3<250::AID-AJMG17>3.0.CO;2-4
  64. Todd, P.K., and Mack, K.J. (2000). Sensory stimulation increases cortical expression of the fragile X mental retardation protein in vivo. Brain Res. Mol. Brain Res. 80, 17-25 https://doi.org/10.1016/S0169-328X(00)00098-X
  65. Tucker, B., Richards, R.I., and Lardelli, M. (2006). Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome. Hum. Mol. Genet. 15, 3446-3458 https://doi.org/10.1093/hmg/ddl422
  66. Turner, G., Webb, T., Wake, S., and Robinson, H. (1996). Prevalence of fragile X syndrome. Am. J. Med. Genet. 64, 196-197 https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<196::AID-AJMG35>3.0.CO;2-G
  67. Valentine, G., Chakravarty, S., Sarvey, J., Bramham, C., and Herkenham, M. (2000). Fragile X (fmr1) mRNA expression is differentially regulated in two adult models of activity-dependent gene expression. Brain Res. Mol. Brain Res. 75, 337-341 https://doi.org/10.1016/S0169-328X(99)00310-1
  68. Van Dam, D., D'Hooge, R., Hauben, E., Reyniers, E., Gantois, I., Bakker, C.E., Oostra, B.A., Kooy, R.F., and De Deyn, P.P. (2000). Spatial learning, contextual fear conditioning and conditioned emotional response in Fmr1 knockout mice. Behav. Brain Res. 117, 127-136 https://doi.org/10.1016/S0166-4328(00)00296-5
  69. Verkerk, A.J., Pieretti, M., Sutcliffe, J.S., Fu, Y.H., Kuhl, D.P., Pizzuti, A., Reiner, O., Richards, S., Victoria, M.F., Zhang, F.P., et al. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65, 905-914 https://doi.org/10.1016/0092-8674(91)90397-H
  70. Volk, L.J., Pfeiffer, B.E., Gibson, J.R., and Huber, K.M. (2007). Multiple Gq-coupled receptors converge on a common protein synthesis-dependent long-term depression that is affected in fragile X syndrome mental retardation. J. Neurosci. 27, 11624- 11634 https://doi.org/10.1523/JNEUROSCI.2266-07.2007
  71. Wang, H., Ku, L., Osterhout, D.J., Li, W., Ahmadian, A., Liang, Z., and Feng, Y. (2004a). Developmentally-programmed FMRP expression in oligodendrocytes: a potential role of FMRP in regulating translation in oligodendroglia progenitors. Hum. Mol. Genet 13, 79-89 https://doi.org/10.1093/hmg/ddh009
  72. Wang, M., Vijayraghavan, S., and Goldman-Rakic, P.S. (2004b). Selective D2 receptor actions on the functional circuitry of working memory. Science 303, 853-856 https://doi.org/10.1126/science.1091162
  73. Wang, H., Wu, L.J., Kim, S.S., Lee, F.J., Gong, B., Toyoda, H., Ren, M., Shang, Y.Z., Xu, H., Liu, F., et al. (2008). FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron 59, 634-647 https://doi.org/10.1016/j.neuron.2008.06.027
  74. Wang, H., Fukushima, H., Kida, S., and Zhuo, M. (2009). Ca2+/ calmodulin-dependent protein kinase IV links group I metabotropic glutamate receptors to fragile X mental retardation protein in cingulate cortex. J. Biol. Chem. 284, 18953-18962 https://doi.org/10.1074/jbc.M109.019141
  75. Weiler, I.J., Irwin, S.A., Klintsova, A.Y., Spencer, C.M., Brazelton, A.D., Miyashiro, K., Comery, T.A., Patel, B., Eberwine, J., and Greenough, W.T. (1997). Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc. Natl. Acad. Sci. USA 94, 5395-5400 https://doi.org/10.1073/pnas.94.10.5395
  76. Wilson, B.M., and Cox, C.L. (2007). Absence of metabotropic glutamate receptor-mediated plasticity in the neocortex of fragile X mice. Proc. Natl. Acad. Sci. USA 104, 2454-2459 https://doi.org/10.1073/pnas.0610875104
  77. Yan, Q.J., Rammal, M., Tranfaglia, M., and Bauchwitz, R.P. (2005). Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49, 1053-1066 https://doi.org/10.1016/j.neuropharm.2005.06.004
  78. Yuen, E.Y., and Yan, Z. (2009). Dopamine D4 receptors regulate AMPA receptor trafficking and glutamatergic transmission in GABAergic interneurons of prefrontal cortex. J. Neurosci. 29, 550-562 https://doi.org/10.1523/JNEUROSCI.5050-08.2009
  79. Zhang, Y.Q., Friedman, D.B., Wang, Z., Woodruff, E., 3rd, Pan, L., O'Donnell, J., and Broadie, K. (2005). Protein expression profiling of the drosophila fragile X mutant brain reveals up-regulation of monoamine synthesis. Mo.l Cell. Proteomics 4, 278-290 https://doi.org/10.1074/mcp.M400174-MCP200
  80. Zhao, M.G., Toyoda, H., Ko, S.W., Ding, H.K., Wu, L.J., and Zhuo, M. (2005). Deficits in trace fear memory and long-term potentiation in a mouse model for fragile X syndrome. J. Neurosci. 25, 7385-7392 https://doi.org/10.1523/JNEUROSCI.1520-05.2005
  81. Zhuo, M. (2008). Cortical excitation and chronic pain. Trends Neurosci. 31, 199-207 https://doi.org/10.1016/j.tins.2008.01.003
  82. Zhuo, M. (2009). Plasticity of NMDA receptor NR2B subunit in memory and chronic pain. Mol. Brain 2, 4 https://doi.org/10.1186/1756-6606-2-4

Cited by

  1. Epigenetics and Biomarkers in the Staging of Neuropsychiatric Disorders vol.18, pp.3, 2010, https://doi.org/10.1007/s12640-010-9163-5
  2. Genetic Controls Balancing Excitatory and Inhibitory Synaptogenesis in Neurodevelopmental Disorder Models vol.2, pp.None, 2009, https://doi.org/10.3389/fnsyn.2010.00004
  3. Conformational-Dependent and Independent RNA Binding to the Fragile X Mental Retardation Protein vol.2011, pp.None, 2009, https://doi.org/10.4061/2011/246127
  4. Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study vol.2, pp.1, 2011, https://doi.org/10.1186/2040-2392-2-6
  5. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning vol.17, pp.5, 2009, https://doi.org/10.1038/nm.2336
  6. Fragile X mental retardation protein is required for programmed cell death and clearance of developmentally-transient peptidergic neurons vol.356, pp.2, 2009, https://doi.org/10.1016/j.ydbio.2011.05.001
  7. In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation vol.21, pp.4, 2009, https://doi.org/10.1093/hmg/ddr527
  8. Commonest Overgrowth Syndromes vol.31, pp.2, 2012, https://doi.org/10.3109/15513815.2011.650293
  9. Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond vol.37, pp.1, 2009, https://doi.org/10.1038/npp.2011.137
  10. Deregulated mTOR-mediated translation in intellectual disability vol.96, pp.2, 2009, https://doi.org/10.1016/j.pneurobio.2012.01.005
  11. Transient expression of Xpn, an XLMR protein related to neurite extension, during brain development and participation in neurite outgrowth vol.214, pp.None, 2009, https://doi.org/10.1016/j.neuroscience.2012.04.030
  12. Hippocampal dysfunction in the Euchromatin histone methyltransferase 1 heterozygous knockout mouse model for Kleefstra syndrome. vol.22, pp.5, 2013, https://doi.org/10.1093/hmg/dds490
  13. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila vol.6, pp.6, 2009, https://doi.org/10.1242/dmm.012229
  14. Identification and Characterisation of Simiate, a Novel Protein Linked to the Fragile X Syndrome vol.8, pp.12, 2013, https://doi.org/10.1371/journal.pone.0083007
  15. Hippocampal synaptic connectivity in phenylketonuria vol.24, pp.4, 2009, https://doi.org/10.1093/hmg/ddu515
  16. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders vol.20, pp.7, 2009, https://doi.org/10.1038/mp.2014.147
  17. The neurobiological basis of sleep: Insights from Drosophila vol.87, pp.None, 2009, https://doi.org/10.1016/j.neubiorev.2018.01.015
  18. Role of fragile X mental retardation protein in chronic pain vol.16, pp.None, 2009, https://doi.org/10.1177/1744806920928619