Tel.: 612-626-3633, Fax: 612-624-8935
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
Version of Record online: 8 SEP 2011
Copyright © 2011 Wiley-Liss, Inc.
The Anatomical Record
Special Issue: Thematic Papers: New Concepts in Developing Brain Disorders—Autism
Volume 294, Issue 10, pages 1635–1645, October 2011
How to Cite
Fatemi, S. H., Folsom, T. D., Kneeland, R. E. and Liesch, S. B. (2011), 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, 294: 1635–1645. doi: 10.1002/ar.21299
- Issue online: 17 SEP 2011
- Version of Record online: 8 SEP 2011
- Manuscript Accepted: 13 MAY 2010
- Manuscript Received: 12 FEB 2010
- National Institute of Child Health and Human Development. Grant Numbers: 5R01HD052074-01A2, 3R01HD052074-03S1
- American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: APA Press.
- 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. , , , , .
- 2003. Levels of Bcl-2 and P53 are altered in superior frontal and cerebellar cortices of autistic subjects. Cell Mol Neurobiol 6: 945–952. , .
- 2000. Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy. Eur J Neurosci 12: 2333–2344. , , , , , .
- 2000. Early development, temperament, and functional impairment in autism and fragile X syndrome. J Autism Dev Disord 30: 557–567. , , , , .
- 2004. The mGluR theory of Fragile X mental retardation. Trends Neurosci 27: 370–377. , , .
- 2009. A pilot open label, single dose of fenobam in adults with Fragile X syndrome. J Med Genet 46: 266–271. , , , , , , , , , , .
- 2008. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr 29: 293–302. , , , , , , , .
- 2005. GABAergic cerebellar system in autism: a neuropathological and developmental perspective. Int Rev Neurobiol 71: 167–178. .
- 2001. Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study. J Aut Dev Disord 31: 537–544. , , , , , .
- 1995. Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers. Brain Res 674: 82–90. , , .
- 1990. Multiple distinct subunits of the γ-aminobutyric acid-A receptor protein show different ligand-binding affinities. Mol Pharmacol 37: 497–502. , .
- 2007. Group I metabotropic glutamate receptors: a role in neurodevelopmental disorders? Mol Neurobiol 35: 298–307. , , , , , .
- 2008. Abnormal striatal GABA transmission in the mouse model for the fragile X syndrome. 63: 963–973. , , , , , , , , , , .
- 1995. Behavioral profiles of autistic and nonautistic fragile X males. Dev Brain Dyn 8: 252–269. .
- 1998. The metabotropic glutamate receptor mGlu5 controls the onset of developmental apoptosis in cultured cerebellar neurons. Eur J Neurosci 10: 2173–2184. , , , , , , , , , , .
- 2000. Reducing conditions differentially affect the functional and structural properties of group-I and -II metabotropic glutamate receptors. Brain Res 867: 156–172. , , , , , , , .
- 1999. Prevalence and phenotype consequence of FRAXA and FRAXE allele in a large ethnically diverse, special education-needs population. Am J Hum Genet 64: 495–507. , , , , , , , , , , , , ,
- 2009. Discrimination of common and unique RNA-binding activities of Fragile X mental retardation protein paralogs. Hum Mol Genet 18: 3164–3177. , , , .
- 2006. Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res 1121: 238–245. , , , , , , .
- 2008. Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia or cerebellar vermal lobules: a potential model of autism spectrum disorder. Behav Brain Res 187: 207–220. , , , , .
- 2010. Fragile X mental retardation protein control of neuronal mRNA metabolism: Insights into mRNA stability. Mol Cell Neurosci 43: 43–50. and .
- 2008. Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of Fragile X syndrome. J Physiol 586: 1503–1508. , .
- 2007. Correction of fragile X syndrome in mice. Neuron 56: 955–962. , , , , , , .
- 2005. Decreased GABAA receptor expression in the seizure-prone fragile X mouse. Neurosci Lett 377: 141–146. , , , , , .
- 2009b. Expression of GABA(B) receptors is altered in brains of Subjects with autism. Cerebellum 8: 64–69. , , , .
- 2001. Altered levels of Bcl-2 and P53 proteins in parietal cortex reflect decreased apoptotic regulation in autism. Synapse 42: 281–284. , .
- 2002a. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in parietal and cerebellar cortices of autistic subjects. Biol Psychiatry 52: 805–810. , , , , , .
- 2009a. GABA(A) Receptor downregulation in brains of subjects with autism. J Autism Dev Disord 39: 223–230. , , , .
- 2010. mRNA and Protein Levels for GABA(A) alpha 4, alpha 5, beta 1, and GABA(B)R1 Receptors are Altered in Brains from Subjects with Autism. J Autism Dev Disord 40: 743–750. , , , , , .
- 2005. Reelin signaling is impaired in autism. Biol Psychiatry 57: 777–787. , , , , , , , ,
- 2002b. Reduced blood levels of Reelin as a vulnerability factor in the pathophysiology of autistic disorder. Cel Mol Neurosci 22: 139–152. , , .
- 1997. Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J Neurosci 17: 1539–1547. , , , , , .
- 2001. Activated astrocytes in areas of kainite-induced neuronal injury upregulate the expression of metabotropic glutamate receptors 2/3 and 5. Exp Brain Res 137: 1–11. , , , , .
- 2006. Past and future perspectives on autism epidemiology. In: Moldin SO, Rubenstein JLR, editors. Understanding autism from basic neuroscience to treatment. Boca Raton, FL: CRC/Taylor and Francis. p 25–48. .
- 2006. Expression profiling suggests underexpression of the GABAA receptor subunit delta in the fragile X knockout mouse model. Neurobiol Dis 21: 346–357. , , , , , , , , .
- 2008. Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiol Dis 30: 303–311. , , , , , , .
- 2008. Neuroanatomy of Fragile X syndrome is associated with aberrant behavior and the Fragile X mental retardation protein (FMRP). Ann Neurol 63: 40–51. , , , , , , , , , , , , , , .
- 2005. Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by positive allosteric modulators. J Biol Chem 280: 24380–24385. , , , , , , , , .
- 2006. Local protein synthesis and spine morphogenesis: Fragile X syndrome and beyond. J Neurosci 26: 7151–7155. , , , .
- 2006. Autistic behavior in children with Fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A 140A: 1804–1813. , , , , , , .
- 2007. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci USA 104: 11489–11494. , , , , , , , .
- 2001. Structural, signaling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors. Biochem J 359: 465–484. , .
- 2005. Fragile X mental retardation protein levels increase following complex environment exposure in rat brain regions undergoing active synaptogenesis. Neurobiol Learn Mem 83: 180–187. , , , , , , , .
- 1943. Autistic disturbances of affective contact. J Nerv Child 2: 217–250. .
- 2004. Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors. Am J Med Genet Part A 129A: 225–234. , , , , , , , , .
- 2007. RNA regulons: coordination of post-translational events. Nat Rev Genet 8: 533–543. .
- 2002. Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells. Cerebellum 1: 19–26. , .
- 2005. Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. Cerebellum 4: 206–210. , .
- 2007. Positive allosteric modulation of metabotropic glutamate 5 (mGlu5) receptors reverses N-methyl-D-aspartate antagonist-induced alteration of neuronal firing in prefrontal cortex. Biol Psychiatry 62: 739–746. , , , .
- 2002. Differential distribution of group I metabotropic glutamate receptors during rat cortical development. Cereb Cortex 12: 625–638. , , , .
- 2004. The Fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development. Proc Natl Acad Sci USA 101: 14374–14378. , , , , , , , .
- 1997. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J Neurosci 17: 5196–5205. , , , , , , .
- 2004. Morphological characteristics of Lugaro cells in the cerebellar cortex. Neurosci Behav Physiol 34: 633–638. , .
- 1999. Cajal-Retzius cells physiology: just in time to bridge the 20th century. Cereb Cortex 9: 776–782. .
- 1999. Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia 40: 1092–1099. , , , , , , , .
- 2005. Crystal structure of the kainite receptor GluR5 ligand-binding core in complex with (S)-glutamate. FEBS Lett 579: 1154–1160. , , , , , .
- 1997. Light and electron microscopic demonstration of mGluR5 metabotropic glutamate receptor immunoreactive neuronal elements in the rat cerebellar cortex. J Comp Neurol 385: 641–650. , , , , , .
- 1996. Metabotropic glutamate receptors mGluR2 and mGluR5 are expressed in two non-overlapping populations of Golgi cells in the rat cerebellum. Neuroscience 75: 815–826. , , , , , .
- 2006. Up-regulation of hippocampal metabotropic glutamate receptor 5 in temporal lobe epilepsy patients. Brain 129: 96–107. , , , , , , .
- 2009. Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism. Autism Res 2: 205–219. , , .
- 1999. The up-regulation of metabotropic glutamate receptor 5 (mGluR5) in Down's syndrome brains. Acta Neuropathol 97: 275–278. , .
- 2009. FMR1: a gene with three faces. Biochem Biophys Acta 1790: 467–477. , .
- 2004. Neuropathological findings in autism. Brain 127: 2572–2583. , , , .
- 2001. Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain. Am J Psychiatry 7: 1058–1066. , , , , , , , , , , .
- 2001. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology 57: 1618–1628. , , , , .
- 2001. Role of excitatory amino acids in developmental epilepsies. Ment Retard Dev Disabil Res Rev 7: 254–260. , , .
- 2008. Autistic disorder. In: Fatemi SH, Clayton P, editors. The medical basis of psychiatry, 3rd ed. New York: Humana Press. p 355–374. , .
- 2001. Covalent and noncovalent interactions mediate metabotropic glutamate receptor mGluR5 dimerization. Mol Pharmacol 59: 46–53. , , , , , , , .
- 1996. Enhance early developmental expression of the metabotropic glutamate receptor mGluR5 in rat brain: protein, mRNA, splice variants, and regional distribution. J Comp Neurol 367: 403–412. , , .
- 2005. Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet 14: 483–492. , , .
- 2002. Homologous sites of GABAA receptor α1, β3, γ2 subunits are important for assembly. Neuropharmacology 43: 482–491. , , , .
- 2007. Regulator of G-protein signaling 4 interacts with metabotropic glutamate receptor 5 in rat striatum: relevance to amphetamine behavioral sensitization. J Pharmacol Exp Ther 323: 650–657. , .
- 2009. A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder. Autism Res 2: 246–257. , , , .
- 2010. Cathespin D and apoptosis related proteins are elevated in the brain of autistic subjects. Neuroscience 165: 363–370. , , , , , .
- 2008. Cerebellar disorders in childhood: cognitive problems. Cerebellum 7: 607–610. .
- 2007. Induction of astrogliosis by activated microglia is associated with a down-regulation of metabotropic glutamate receptor 5. J Neuroimmunol 189: 23–30. , , .
- 2005. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57: 67–81. , , , , .
- 2009. Norbin in an endogenous regulator of metabotropic glutamate receptor 5 signaling. Science 326: 1554–1557. , , , , , , , , , .
- 2009. Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder. Psychiatry Res 172: 61–67. , , , , , , .
- 2007. Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications. Acta Neuropathologica 113: 559–568. , , .