Top

Optie A:

Klik op de rechtermuisknop op de link en selecteer de optie “linkadres kopiëren”
Optie B:

Deel de link per e-mail
Link delen

vorige artikel Does Nutritional Intake Differ Between Children...

volgende artikel Sensori-motor and Daily Living Skills of Presch...

Tip

Swipe om te navigeren naar een ander artikel

01-02-2009 | Original Paper | Uitgave 2/2009

GABA_A Receptor Downregulation in Brains of Subjects with Autism

Tijdschrift:: Journal of Autism and Developmental Disorders > Uitgave 2/2009

Auteurs:: S. Hossein Fatemi, Teri J. Reutiman, Timothy D. Folsom, Paul D. Thuras

» Toegang tot de volledige tekst krijgen

Abstract

Gamma-aminobutyric acid A (GABA_A) receptors are ligand-gated ion channels responsible for mediation of fast inhibitory action of GABA in the brain. Preliminary reports have demonstrated altered expression of GABA receptors in the brains of subjects with autism suggesting GABA/glutamate system dysregulation. We investigated the expression of four GABA_A receptor subunits and observed significant reductions in GABRA1, GABRA2, GABRA3, and GABRB3 in parietal cortex (Brodmann’s Area 40 (BA40)), while GABRA1 and GABRB3 were significantly altered in cerebellum, and GABRA1 was significantly altered in superior frontal cortex (BA9). The presence of seizure disorder did not have a significant impact on GABA_A receptor subunit expression in the three brain areas. Our results demonstrate that GABA_A receptors are reduced in three brain regions that have previously been implicated in the pathogenesis of autism, suggesting widespread GABAergic dysfunction in the brains of subjects with autism.

Log in om toegang te krijgen

Hier inloggen

Met onderstaand(e) abonnement(en) heeft u direct toegang:

BSL Psychologie Totaal

Met BSL Psychologie Totaal blijf je als professional steeds op de hoogte van de nieuwste ontwikkelingen binnen jouw vak. Met het online abonnement heb je toegang tot een groot aantal boeken, protocollen, vaktijdschriften en e-learnings op het gebied van psychologie en psychiatrie. Zo kun je op je gemak en wanneer het jou het beste uitkomt verdiepen in jouw vakgebied.

Meer informatie

Abdolmaleky, H. M., Cheng, K. H., Russo, A., Smith, C. L., Faraone, S. V., Wilcox, M., et al. (2005). Hypermethylation of the Reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 134B, 60–66. doi: 10.1002/ajmg.b.30140. CrossRef

Akbarian, S., Kim, J. J., Potkin, S. G., Hagman, J. O., Tafazzoli, A., Bunney, W. E., Jr., et al. (1995). Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Archives of General Psychiatry, 52, 258–266. PubMed

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: APA Press.

Bauman, M. L., & Kemper, T. L. (Eds.). (1994). Neuroanatomic observations of the brain in autism. In The neurobiology of autism (pp. 19–145). Baltimore, MD: Johns Hopkins University Press.

Bauman, M. L., & Kemper, T. L. (Eds.). (2005). Structural brain anatomy in autism: What is the evidence? In The neurobiology of autism (pp. 121–135). Baltimore, MD: Johns Hopkins University Press.

Binnie, C. D. (1993). Significance and management of transitory cognitive impairment due to subclinical EEG discharges in children. Brain and Development, 15, 23–30.

Blatt, G. J., Fitzgerald, C. M., Guptill, J. T., Booker, A. B., Kemper, T. L., & Bauman, M. L. (2001). Density and distribution of hippocampal neurotransmitter receptors in autism: An autoradiographic study. Journal of Autism and Developmental Disorders, 31, 537–544. doi: 10.1023/A:1013238809666. PubMedCrossRef

Brandon, N. J., Smart, T. G., & Moss, S. J. (2000). Regulation of GABAA receptors by protein phosphorylation. In D. Martin & R. Olsen (Eds.), GABA in the nervous system: The view at fifty years (pp. 191–206). Philadelphia, PA: Lippincott, Williams and Wilkins.

Buxhoeveden, D. P., Semendeferi, K., Schenker, N., & Courchesne, E. (2004). Decreased cell column spacing in autism. Program and abstracts of the Society for Neuroscience 34th Annual Meeting, San Diego, California. Abstract 582.6.

Canitano, R. (2007). Epilepsy in autism spectrum disorders. European Child and Adolescent Psychiatry, 16, 61–66.

Carper, R., & Courchesne, E. (2005). Localized enlargement of the frontal lobe in autism. Biological Psychiatry, 57, 126–133. doi: 10.1016/j.biopsych.2004.11.005. PubMedCrossRef

Carper, R. A., Moses, P., Tigue, Z. D., & Courchesne, E. (2002). Cerebral lobes in autism: Early hyperplasia and abnormal age effects. NeuroImage, 16, 1038–1051. doi: 10.1006/nimg.2002.1099. PubMedCrossRef

Casanova, M. F., Buxhoeveden, D. P., & Brown, C. (2002). Clinical and macroscopic correlates of minicolumnar pathology in autism. Journal of Child Neurology, 17, 692–695.

Courchesne, E., & Pierce, K. (2005). Why the frontal cortex in autism might be talking only to itself: Local over-connectivity but long-distance disconnection. Current Opinion in Neurobiology, 15, 225–230. doi: 10.1016/j.conb.2005.03.001. PubMedCrossRef

Courchesne, E., Press, G. A., & Young-Courchesne, R. (1993). Parietal lobe abnormalities detected with MR in patients with infantile autism. AJR American Journal of Roentgenology, 160, 387–393. PubMed

DeLorey, T. M., Handforth, A., Anagnostaras, S. G., Homanics, G. E., Minassian, B. A., Asatourian, A., et al. (1998). Mice lacking the beta 3 subunit of the GABA _A receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome. The Journal of Neuroscience, 18, 8505–8514. PubMed

DeLorey, T. M., Sahbaie, P., Hashemi, E., Homanics, G. E., & Clark, J. D. (2008). Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder. Behavioural Brain Research, 187, 207–220. doi: 10.1016/j.bbr.2007.09.009. PubMedCrossRef

Dhossche, D., Applegate, H., Abraham, A., Maertens, P., Bland, L., Bencsath, A., et al. (2002). Elevated plasma gama-aminobutyric acid (GABA) levels in autistic youngsters: Stimulus for GABA hypothesis of autism. Medical Science Monitor, 8, PR1–PR6. PubMed

Fatemi, S. H. (2008). The hyperglutamatergic hypothesis of autism. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32, 911.

Fatemi, S. H., Halt, A. R., Earle, J., Kist, D. A., Realmuto, G. R., Thuras, P. D., et al. (2000). Reduced Purkinje cell size in autistic cerebellum. Biological Psychiatry, 47, S128. doi: 10.1016/S0006-3223(00)00687-9. CrossRef

Fatemi, S. H., Halt, A. R., Realmuto, G., Earle, J., Kist, D. A., Thuras, P., et al. (2002b). Purkinje cell size is reduced in cerebellum of patients with autism. Cellular and Molecular Neurobiology, 22, 171–175. doi: 10.1023/A:1019861721160. PubMedCrossRef

Fatemi, S. H., Halt, A., Stary, J., Kanodia, R., Schulz, S. C., & Realmuto, G. (2002a). Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in parietal and cerebellar cortices of autistic subjects. Biological Psychiatry, 52, 805–810. doi: 10.1016/S0006-3223(02)01430-0. PubMedCrossRef

Fatemi, S. H., Stary, J. M., Earle, J. A., Araghi-Niknam, M., & Eagan, E. (2005). GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum. Schizophrenia Research, 72, 109–122. doi: 10.1016/j.schres.2004.02.017. PubMedCrossRef

Grayson, D. R., Chen, Y., Costa, E., Dong, E., Guidotti, A., Kundakovic, M., et al. (2006). The human Reelin gene: Transcription factors (+), repressors (−) and the methylation switch (+/−) in schizophrenia. Pharmacology & Therapeutics, 111, 272–286. doi: 10.1016/j.pharmthera.2005.01.007. CrossRef

Grayson, D. R., Jia, X., Chen, Y., Sharma, R. P., Mitchell, C. P., Guidotti, A., et al. (2005). Reelin promoter hypermethylation in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 102, 9341–9346. doi: 10.1073/pnas.0503736102. PubMedCrossRef

Guidotti, A., Auta, J., Davis, J. M., Di-Giorgi-Gerevini, V., Dwivedi, Y., Grayson, D. R., et al. (2000). Decrease in Reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: A postmortem brain study. Archives of General Psychiatry, 57, 1061–1069. doi: 10.1001/archpsyc.57.11.1061. PubMedCrossRef

Guptill, J. T., Booker, A. B., Gibbs, T. T., Kemper, T. L., Bauman, M. L., & Blatt, G. J. (2007). [3H]-flunitrazepam-labeled benzodiazepine binding sites in the hippocampal formation in autism: A multiple concentration autoradiographic study. Journal of Autism and Developmental Disorder, 37, 911–920.

Haas, R. H., Townsend, J., Courchesne, E., Lincoln, A. J., Schreibman, L., & Young-Courchesne, R. (1996). Neurologic abnormalities in infantile autism. Journal of Child Neurology, 11, 84–92. PubMedCrossRef

Hakak, Y., Walker, J. R., Li, C., Wong, W. H., Davis, K. L., Buxbaum, J. D., et al. (2001). Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 98, 4746–4751. doi: 10.1073/pnas.081071198. PubMedCrossRef

Hogart, A., Nagarajan, R. P., Patzel, K. A., Yasui, D. H., & Lasalle, J. M. (2007). 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Human Molecular Genetics, 16, 691–703. doi: 10.1093/hmg/ddm014. PubMedCrossRef

Homanics, G. E., DeLorey, T. M., Firestone, L. L., Quinlan, J. J., Handforth, A., Harrison, N. L., et al. (1997). Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proceedings of the National Academy of Sciences of the United States of America, 94, 4143–4148. doi: 10.1073/pnas.94.8.4143. PubMedCrossRef

Inada, T., Koga, M., Ishiguro, H., Horiuchi, Y., Syu, A., Yoshio, T., et al. (2008). Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia. Pharmacogenetics and Genomics, 18, 317–323. doi: 10.1097/FPC.0b013e3282f70492. PubMedCrossRef

Kakinuma, H., Ozaki, M., Sato, H., & Takahashi, H. (2007). Variation in GABA-A subunit gene copy number in an autistic patient with mosaic 4p duplication. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 147B, 973–975.

Kim, S. A., Kim, J. H., Park, M., Cho, I. H., & Yoo, H. J. (2006). Association of GABRB3 polymorphisms with autism spectrum disorders in Korean trios. Neuropsychobiology, 54, 160–165. doi: 10.1159/000098651. PubMedCrossRef

Ma, D. Q., Whitehead, P. L., Menold, M. M., Martin, E. R., Ashley-Koch, A. E., Mei, H., et al. (2005). Identification of significant association and gene–gene interaction of GABA receptor subunit genes in autism. American Journal of Human Genetics, 77, 377–388. doi: 10.1086/433195. PubMedCrossRef

McCauley, J. L., Olson, L. M., Delahanty, R., Amin, T., Nurmi, E. L., Organ, E. L., et al. (2004). A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 131, 51–59.

Nayate, A., Bradshaw, J. L., & Rinehart, N. J. (2005). Autism and Asperger’s disorder: Are they movement disorders involving the cerebellum and/or basal ganglia? Brain Research Bulletin, 67, 327–334. doi: 10.1016/j.brainresbull.2005.07.011. PubMedCrossRef

Ohnuma, T., Augood, S. J., Arai, H., McKenna, P. J., & Emson, P. C. (1999). Measurement of GABAergic parameters in the prefrontal cortex in schizophrenia: Focus on GABA content, GABA(A) receptor alpha-1 subunit messenger RNA and human GABA transporter-1 (HGAT-1) messenger RNA expression. Neuroscience, 93, 441–448. doi: 10.1016/S0306-4522(99)00189-X. PubMedCrossRef

Palmen, S. J., van Engeland, H., Hof, P. R., & Schmitz, C. (2004). Neuropathological findings in autism. Brain, 127, 2572–2583. doi: 10.1093/brain/awh287. PubMedCrossRef

Persico, A. M., & Bourgeron, T. (2006). Searching for ways out of the autism maze: Genetic, epigenetic and environmental clues. Trends in Neurosciences, 29, 349–358. doi: 10.1016/j.tins.2006.05.010. PubMedCrossRef

Purcell, A. E., Jeon, O. H., Zimmerman, A. W., Blue, M. E., & Pevsner, J. (2001). Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology, 57, 1618–1628. PubMed

Ritvo, E. R., Freeman, B. J., Scheibel, A. B., Duong, T., Robinson, H., Guthrie, D., et al. (1986). Lower Purkinje cell counts in the cerebella of four autistic subjects: Initial findings of the UCLA-NSAC autopsy research repot. The American Journal of Psychiatry, 143, 862–866. PubMed

Saitoh, O., & Courchesne, E. (1998). Magnetic resonance imaging study of the brain in autism. Psychiatry and Clinical Neurosciences, 52, S219–S222. doi: 10.1111/j.1440-1819.1998.tb01040.x. PubMedCrossRef

Samaco, R. C., Hogart, A., & LaSalle, J. M. (2005). Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Human Molecular Genetics, 14, 483–492. doi: 10.1093/hmg/ddi045. PubMedCrossRef

Schroer, R. J., Phelan, M. C., Michaelis, R. C., Crawford, E. C., Skinner, S. A., Cuccaro, M., et al. (1998). Autism and maternally derived aberrations of chromosome 15q. American Journal of Medical Genetics, 76, 327–336. doi:10.1002/(SICI)1096-8628(19980401)76:4<327::AID-AJMG8>3.0.CO;2-M. PubMedCrossRef

Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G., et al. (1989). A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. Journal of Child Psychology and Psychiatry and Allied Disciplines, 30, 405–416. doi: 10.1111/j.1469-7610.1989.tb00254.x. CrossRef

Tochigi, M., Kato, C., Koishi, S., Kawakubo, Y., Yamamoto, K., Matsumoto, H., et al. (2007). No evidence for significant association between GABA receptor genes in chromosome. Journal of Human Genetics, 52, 985–989. doi: 10.1007/s10038-007-0207-5. PubMedCrossRef

Townsend, J., Harris, D. L., & Courchesne, E. (1996). Visual attention abnormalities in autism: Delayed orienting to location. Journal of the International Neuropsychological Society, 2, 541–550. PubMedCrossRef

Tuchman, R., & Rapin, I. (2002). Epilepsy in autism. Lancet Neurology, 1, 352–358.

Yip, J., Soghomonian, J. J., & Blatt, G. J. (2007). Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: Pathophysiological implications. Acta Neuropathologica, 113, 559–568. doi: 10.1007/s00401-006-0176-3. PubMedCrossRef

Titel: GABAA Receptor Downregulation in Brains of Subjects with Autism
Auteurs:: S. Hossein Fatemi
Teri J. Reutiman
Timothy D. Folsom
Paul D. Thuras
Publicatiedatum: 01-02-2009
DOI: https://doi.org/10.1007/s10803-008-0646-7
Uitgeverij: Springer US
Tijdschrift: Journal of Autism and Developmental Disorders
Uitgave 2/2009
Print ISSN: 0162-3257
Elektronisch ISSN: 1573-3432

Bohn Stafleu van Loghum

Deel dit onderdeel of sectie (kopieer de link)

Tip

Swipe om te navigeren naar een ander artikel

GABA_A Receptor Downregulation in Brains of Subjects with Autism

Abstract

Log in om toegang te krijgen

Met onderstaand(e) abonnement(en) heeft u direct toegang:

BSL Psychologie Totaal

Bohn Stafleu van Loghum

Deel dit onderdeel of sectie (kopieer de link)

Tip

Swipe om te navigeren naar een ander artikel

Abstract

Log in om toegang te krijgen

Met onderstaand(e) abonnement(en) heeft u direct toegang:

BSL Psychologie Totaal

Andere artikelen Uitgave 2/2009

Functional Assessment of Problem Behavior in Children with Autism Spectrum Disorders: A Summary of 32 Outpatient Cases

Pleiotropic Effects of Neurotransmission during Development: Modulators of Modularity

Sensori-motor and Daily Living Skills of Preschool Children with Autism Spectrum Disorders

A Specific Autistic Trait that Modulates Visuospatial Illusion Susceptibility

A Novel 6.14 Mb Duplication of Chromosome 8p21 in a Patient with Autism and Self Mutilation

Brief Report: Pragmatic Language in Autism Spectrum Disorder: Relationships to Measures of Ability and Disability