Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study

Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, Kooy F, Willems PJ, Cras P, Kozlowski PB, Swain RA, Weiler IJ, Greenough WT: Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet. 2001, 98: 161-167. 10.1002/1096-8628(20010115)98:2<161::AID-AJMG1025>3.0.CO;2-B. Gothelf D, Furfaro JA, Hoeft F, Eckert MA, Hall SS, O'Hara R, Erba HW, Ringel J, Hayashi KM, Patnaik S, Golianu B, Kraemer HC, Thompson PM, Piven J, Reiss AL: Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP). Ann Neurol. 2008, 63: 40-51. 10.1002/ana.21243. Hallahan B, Daly EM, McAlonan G, Loth E, Toal F, O'Brien F, Robertson D, Hales S, Murphy C, Murphy KC, Murphy DG: Brain morphometry volume in autistic spectrum disorder: a magnetic resonance imaging study of adults. Psychol Med. 2008, 39: 337-346. Hutsler JJ, Zhang H: Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res. 2010, 1309: 83-94. Hatton DD, Sideris J, Skinner M, Mankowski J, Bailey DB, Roberts J, Mirrett P: Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A. 2006, 140A: 1804-1813. 10.1002/ajmg.a.31286. Bailey DB, Mesibov GB, Hatton D, Clark RD, Roberts JE, Mayhew L: Autistic behavior in young boys with fragile X syndrome. J Autism Dev Disord. 1998, 28: 499-508. 10.1023/A:1026048027397. Kau AS, Tierney E, Bukelis I, Stump MH, Kates WR, Trescher WH, Gray RM, Cox C, Capone GT, Stanard P: Social behavior profile in young males with fragile X syndrome: Characteristics and specificity. Am J Med Genet A. 2004, 126A: 9-17. 10.1002/ajmg.a.20218. Philofsky A, Hepburn SL, Hayes A, Hagerman RJ, Rogers SJ: Linguistic and cognitive functioning and autism symptoms in young children with fragile X syndrome. Am J Ment Retard. 2004, 109: 208-218. 10.1352/0895-8017(2004)109<208:LACFAA>2.0.CO;2. Roberts JE, Boccia ML, Bailey DB, Hatton DD, Skinner M: Cardiovascular indices of physiological arousal in boys with fragile X syndrome. Dev Psychobiol. 2001, 39: 107-123. 10.1002/dev.1035. Chudley AE, Gutierrez E, Jocelyn LJ, Chodirker BN: Outcomes of genetic evaluation in children with pervasive developmental disorder. J Dev Behav Pediatr. 1998, 19: 321-325. 10.1097/00004703-199810000-00001. Wassink TH, Piven J, Patil SR: Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr Genet. 2001, 11: 57-63. 10.1097/00041444-200106000-00001. Bailey DB, Hatton DD, Mesibov GB, Ament N, Skinner M: Early development, temperament, and functional impairment in autism and fragile X syndrome. J Autism Dev Disord. 2000, 30: 557-567. Kauffman WE, Cortell R, Kau A, Bukelis I, Tierney E, Gray R, Cox C, Capone G, Stanard P: Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors. Am J Med Genet A. 2004, 129A: 225-234. 10.1002/ajmg.a.30229. Hall SS: Treatments for fragile X syndrome: a closer look at the data. Dev Disabil Res Rev. 2009, 15: 353-360. 10.1002/ddrr.78. De Rubeis S, Bagni C: Fragile X mental retardation protein control of neuronal mRNA metabolism: Insights into mRNA stability. Mol Cell Neurosci. 2010, 43: 43-50. 10.1016/j.mcn.2009.09.013. Keene JD: RNA regulons: Coordination of post-translational events. Nat Rev Genet. 2007, 8: 533-543. 10.1038/nrg2111. Bassell GJ, Warren ST: Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron. 2008, 60: 201-214. 10.1016/j.neuron.2008.10.004. Till SM: The developmental roles of FMRP. Biochem Soc Trans. 2010, 38: 507-510. 10.1042/BST0380507. Pfeiffer BE, Huber KM: Fragile X mental retardation protein induces synapse loss through acute postsynaptic translational regulation. J Neurosci. 2007, 27: 3120-3130. 10.1523/JNEUROSCI.0054-07.2007. Mercaldo V, Descalzi G, Zhuo M: Fragile X mental retardation protein in learning-related synaptic plasticity. Mol Cells. 2009, 28: 501-507. 10.1007/s10059-009-0193-x. Brown V, Jin P, Ceman S, Darnell JC, O'Donnell WT, Tenenbaum SA, Jin X, Feng Y, Wilkinson KD, Keene JD, Darnell RB, Warren ST: Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell. 2001, 107: 477-487. 10.1016/S0092-8674(01)00568-2. El Idrissi A, Ding XH, Scalia J, Trenkner E, Brown WT, Dobkin C: Decreased GABAA receptor expression in the seizure-prone fragile X mouse. Neurosci Lett. 2005, 377: 141-146. 10.1016/j.neulet.2004.11.087. D'Hulst C, De Geest N, Reeve SP, Van Dam D, De Deyn PP, Hassan BA, Kooy RF: Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res. 2006, 1121: 238-245. 10.1016/j.brainres.2006.08.115. Gantois I, Vandescompele J, Speleman F, Reyniers E, D'Hooge R, Severijnen LA, Willemsen R, Tassone F, Kooy RF: Expression profiling suggests underexpression of the GABAA receptor subunit delta in the fragile X knockout mouse model. Neurobiol Dis. 2006, 21: 346-357. 10.1016/j.nbd.2005.07.017. Fatemi SH, Folsom TD, Kneeland RE, Liesch SB: Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. Anat Rec. Fatemi SH, Reutiman TJ, Folsom TD, Thuras PD: GABAA receptor downregulation in brains of subjects with autism. J Autism Dev Disord. 2009, 39: 223-230. 10.1007/s10803-008-0646-7. Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD: Expression of GABAB receptors is altered in brains of subjects with autism. Cerebellum. 2009, 8: 64-69. 10.1007/s12311-008-0075-3. Fatemi SH, Reutiman TJ, Folsom TD, Rooney RJ, Patel DH, Thuras PD: mRNA and Protein levels for GABAA alpha 4, alpha 5, beta 1, and GABABR1 receptors are altered in brains from subjects with autism. J Autism Dev Disord. 2010, 40: 743-750. 10.1007/s10803-009-0924-z. Bureau M, Olsen RW: Multiple distinct subunits of the γ-aminobutyric acid-A receptor protein show different ligand-binding affinities. Mol Pharmacol. 1990, 37: 497-502. Samaco RC, Hogart A, LaSalle JM: Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet. 2005, 14: 483-492. Sarto I, Wabnegger L, Dogl E, Sieghart W: Homologous sites of GABAA receptor α1, β3, γ2 subunits are important for assembly. Neuropharmacology. 2002, 43: 482-491. 10.1016/S0028-3908(02)00160-0. Cohen J: A power primer. Psychol Bull. 1992, 112: 155-159. Darnell JC, Fraser CE, Mostovetsky O, Darnell RB: Discrimination of common and unique RNA-binding activities among fragile X mental retardation protein paralogs. Hum Mol Genet. 2009, 18: 3164-3177. 10.1093/hmg/ddp255. Sittler A, Devys D, Weber C, Mandel JC: Alternative splicing of exon 14 determines nuclear or cytoplasmic localization of fmr1 protein isoforms. Hum Mol Genet. 1996, 5: 95-102. 10.1093/hmg/5.1.95. Menon V, Kwon H, Eliez S, Taylor AK, Reiss AL: Functional brain activation during cognition is related to FMR1 gene expression. Brain Res. 2000, 877: 367-370. 10.1016/S0006-8993(00)02617-2. Hoeft F, Hernandez A, Parthasarathy S, Watson CL, Hall SS, Reiss AL: Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome. Hum Brain Mapp. 2007, 28: 543-554. 10.1002/hbm.20406. Rivera SM, Menon V, White CD, Glaser B, Reiss AL: Functional brain activation during arithmetic processing in females with fragile X syndrome is related to FMR1 protein expression. Hum Brain Mapp. 2002, 16: 206-218. 10.1002/hbm.10048. Huang YY, Simpson E, Kellendonk C, Kandel ER: Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors. Proc Natl Acad Sci USA. 2004, 101: 3236-3241. 10.1073/pnas.0308280101. Surmeier DJ: Dopamine and working memory mechanisms in prefrontal cortex. J Physiol. 2007, 581: 885-10.1113/jphysiol.2007.134502. Wang H, Wu LJ, Kim SS, Lee FJ, Gong B, Toyoda H, Ren M, Shang YZ, Xu H, Liu F, Zhao MG, Zhuo M: FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron. 2008, 59: 634-647. 10.1016/j.neuron.2008.06.027. Wang H, Kim SS, Zhuo M: Roles of fragile X mental retardation protein in dopaminergic stimulation-induced synapse-associated protein synthesis and subsequent alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-proprionate (AMPA) receptor internalization. J Biol Chem. 2010, 285: 21888-21901. 10.1074/jbc.M110.116293. Laurence JA, Fatemi SH: Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. Cerebellum. 2005, 4: 206-210. 10.1080/14734220500208846. Rosengren LE, Ahlsen G, Belfrage M, Gillberg C, Haglid KG, Hamberger A: A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children. J Neurosci Methods. 1992, 44: 113-119. 10.1016/0165-0270(92)90004-W. Ahlsen G, Rosengren L, Belfrage M, Palm A, Haglid K, Hamberger A, Gillberg C: Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry. 1993, 33: 734-743. 10.1016/0006-3223(93)90124-V. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA: Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005, 57: 67-81. 10.1002/ana.20315. Pacey LK, Doering LC: Developmental expression of FMRP in the astrocyte lineage: implications for fragile X syndrome. Glia. 2007, 55: 1601-1609. 10.1002/glia.20573. Price TJ, Rashid MH, Millecamps M, Sanoja R, Entrena JM, Cervero F: Decreased nociceptive sensitization in mice lacking fragile X mental retardation protein: role of mGluR1/5 and mTOR. J Neurosci. 2007, 27: 13958-13967. 10.1523/JNEUROSCI.4383-07.2007. Ellegood J, Pacey LK, Hampson DR, Lerch JP, Henkelman RM: Anatomical phenotyping in a mouse model of fragile X syndrome with magnetic resonance imaging. NeuroImage. 2010, 53: 1023-1029. 10.1016/j.neuroimage.2010.03.038. Yuskaitis CJ, Beurel E, Jope RS: Evidence of reactive astrocytes but not peripheral immune system activation in a mouse model of fragile X syndrome. Biochim Biophys Acta. 2010, 1802: 1006-1012. Bear MF, Huber KM, Warren ST: The mGluR theory of fragile X mental retardation. Trends Neurosci. 2004, 27: 370-377. 10.1016/j.tins.2004.04.009. Dölen G, Osterweil E, Shankaranarayana Rao BS, Smith GB, Auerbach D, Chattarji S, Bear MF: Correction of fragile X syndrome in mice. Neuron. 2007, 56: 955-962. 10.1016/j.neuron.2007.12.001. Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP: Suppression of two major fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropsychopharmacology. 2005, 49: 1053-1066. de Vrij FM, Levenga J, van der Linde HC, Koekkoek SK, De Zeeuw CI, Nelson DL, Oostra BA, Willemsen R: Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis. 2008, 31: 127-132. 10.1016/j.nbd.2008.04.002. Silverman JL, Tolu SS, Barkan CL, Crawley JN: Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP. Neurospsychopharmacology. 2010, 35: 976-989. 10.1038/npp.2009.201. Silverman JL, Yang M, Turner SM, Katz AM, Bell DB, Koenig JI, Crawley JN: Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism. Neuroscience. 2010, 171: 1197-1208. 10.1016/j.neuroscience.2010.09.059. Berry-Kravis E, Sumis A, Hervey C, Nelson M, Porges SW, Weng N, Weiler IJ, Greenough WT: Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr. 2008, 29: 293-302. 10.1097/DBP.0b013e31817dc447. Porter RH, Jaeschke G, Spooren W, Ballard TM, Büttelmann B, Kolczewski S, Peters JU, Prinssen E, Wichmann J, Vieira E, Mühlemann A, Gatti S, Mutel V, Malherbe P: Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity. J Pharmacol Exp Ther. 2005, 315: 711-721. 10.1124/jpet.105.089839. Berry-Kravis E, Hessl D, Coffey S, Hervey C, Schneider A, Yuhas J, Hutchison J, Snape M, Tranfaglia M, Nguyen DV, Hagerman R: A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J Med Genet. 2009, 46: 266-271. 10.1136/jmg.2008.063701. Wang H, Westin L, Nong Y, Birnbaum S, Bendor J, Brismar H, Nestler E, Aperia A, Flajolet M, Greengard P: Norbin in an endogenous regulator of metabotropic glutamate receptor 5 signaling. Science. 2009, 326: 1554-1557. 10.1126/science.1178496. Heulens I, D'Hulst C, Braat S, Rooms L, Koory RF: Involvement and therapeutic potential of the GABAergic system in the fragile X syndrome. ScientificWorldJournal. 2010, 10: 2198-2206. Fatemi SH, Folsom TD: The role of fragile X mental retardation protein in major mental disorders. Neuropharmacology. 2011, 60: 1221-1226. 10.1016/j.neuropharm.2010.11.011.