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Gepubliceerd in: Journal of Autism and Developmental Disorders 5/2007

01-05-2007 | Original Paper

[3H]-Flunitrazepam-labeled Benzodiazepine Binding Sites in the Hippocampal Formation in Autism: A Multiple Concentration Autoradiographic Study

Auteurs: Jeffrey T. Guptill, Anne B. Booker, Terrell T. Gibbs, Thomas L. Kemper, Margaret L. Bauman, Gene J. Blatt

Gepubliceerd in: Journal of Autism and Developmental Disorders | Uitgave 5/2007

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Abstract

Increasing evidence indicates that the GABAergic system in cerebellar and limbic structures is affected in autism. We extended our previous study that found reduced [3H]flunitrazepam-labeled benzodiazepine sites in the autistic hippocampus to determine whether this reduction was due to a decrease in binding site number (B max) or altered affinity (K d) to bind to the ligand. Quantitation of hippocampal lamina demonstrated a 20% reduction in B max indicating a trend toward a decreased number of benzodiazepine binding sites in the autistic group but normal K d values. A reduction in the number of hippocampal benzodiazepine binding sites suggests alterations in the modulation of GABAA receptors in the presence of GABA in the autistic brain, possibly resulting in altered inhibitory functioning of hippocampal circuitry.
Literatuur
go back to reference American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders ( DSM-IV) (4th ed.). Washington, DC: American Psychiatric Press. American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders ( DSM-IV) (4th ed.). Washington, DC: American Psychiatric Press.
go back to reference Arin, D. M., Bauman, M. L., & Kemper, T. L. (1991). The distribution of Purkinje cell loss in the cerebellum in autism (abstract). Neurology, 41, 307. Arin, D. M., Bauman, M. L., & Kemper, T. L. (1991). The distribution of Purkinje cell loss in the cerebellum in autism (abstract). Neurology, 41, 307.
go back to reference Babb, T. L., Pretorius, J. K., Kupfer, W. R., & Crandell, P. H. (1989) Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus. Journal of Neuroscience, 9, 2562–2574. PubMed Babb, T. L., Pretorius, J. K., Kupfer, W. R., & Crandell, P. H. (1989) Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus. Journal of Neuroscience, 9, 2562–2574. PubMed
go back to reference Bailey, A., Luthert, P., Dean, A., Harding, B., Janota, I., Montgomery, M., Rutter, M., & Lantos, P. (1998). A clinicopathological study of autism. Brain, 121, 889–905. PubMedCrossRef Bailey, A., Luthert, P., Dean, A., Harding, B., Janota, I., Montgomery, M., Rutter, M., & Lantos, P. (1998). A clinicopathological study of autism. Brain, 121, 889–905. PubMedCrossRef
go back to reference Barker, J. L., Behar, T. N., Ma, W., Maric, D., & Maric, I. (2000). GABA emerges as a developmental signal during neurogenesis of the rat central nervous system. In D. L. Martin, & R. W. Olsen (Eds.), GABA in the nervous system: The view at fifty years (pp. 245–263, Ch. 15). Philadelphia: Lippincott Williams and Wilkins. Barker, J. L., Behar, T. N., Ma, W., Maric, D., & Maric, I. (2000). GABA emerges as a developmental signal during neurogenesis of the rat central nervous system. In D. L. Martin, & R. W. Olsen (Eds.), GABA in the nervous system: The view at fifty years (pp. 245–263, Ch. 15). Philadelphia: Lippincott Williams and Wilkins.
go back to reference Bauman, M. L., & Kemper, T. L. (1994). Neuroanatomic observations of the brain in autism. In M. L. Bauman, & T. L. Kemper (Eds.), The Neurobiology of autism (pp. 119–145). Baltimore: Johns Hopkins University Press. Bauman, M. L., & Kemper, T. L. (1994). Neuroanatomic observations of the brain in autism. In M. L. Bauman, & T. L. Kemper (Eds.), The Neurobiology of autism (pp. 119–145). Baltimore: Johns Hopkins University Press.
go back to reference Bauman, M. L., & Kemper, T. L. (1985). Histoanatomic observations of the brain in early infantile autism. Neurology, 35, 866–874. PubMed Bauman, M. L., & Kemper, T. L. (1985). Histoanatomic observations of the brain in early infantile autism. Neurology, 35, 866–874. PubMed
go back to reference 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, 537–543. PubMedCrossRef 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, 537–543. PubMedCrossRef
go back to reference Dennis, T., Dubois, A., Benavides, J., & Scatton, B. (1988). Distribution of central ω 1 (benzodiazepine 1) and ω 2 (benzodiazepine 2) receptor subtypes in the monkey and human brain. An autoradiographic study with [ 3H]flunitrazepam and the ω 1 selective ligand [ 3H]zolpidem. Journal of Pharmacolology and Experimental Therapeutics, 247, 309–322. Dennis, T., Dubois, A., Benavides, J., & Scatton, B. (1988). Distribution of central ω 1 (benzodiazepine 1) and ω 2 (benzodiazepine 2) receptor subtypes in the monkey and human brain. An autoradiographic study with [ 3H]flunitrazepam and the ω 1 selective ligand [ 3H]zolpidem. Journal of Pharmacolology and Experimental Therapeutics, 247, 309–322.
go back to reference Fatemi, S. H., Halt, A. R., Stary, J. M., Kanodia, R., Schulz, S. C., & Realmuto, G. R. (2002). Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biological Psychiatry, 52, 805–810. PubMedCrossRef Fatemi, S. H., Halt, A. R., Stary, J. M., Kanodia, R., Schulz, S. C., & Realmuto, G. R. (2002). Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biological Psychiatry, 52, 805–810. PubMedCrossRef
go back to reference Freund, J. (1988). Analysis of variance. In N. Romanelli (Ed.), Modern elementary statistics (7th ed., pp. 380–414). Englewood Cliffs: Prentice Hall. Freund, J. (1988). Analysis of variance. In N. Romanelli (Ed.), Modern elementary statistics (7th ed., pp. 380–414). Englewood Cliffs: Prentice Hall.
go back to reference Fritschy, J.-M., Kiener, T., Bouilleret, V., & Loup, F. (1999). GABAergic neurons and GABAA-receptors in temporal lobe epilepsy. Neurochemistry International, 34, 435–445. PubMedCrossRef Fritschy, J.-M., Kiener, T., Bouilleret, V., & Loup, F. (1999). GABAergic neurons and GABAA-receptors in temporal lobe epilepsy. Neurochemistry International, 34, 435–445. PubMedCrossRef
go back to reference Fritschy, J.-M., & Brunig, I. (2003). Formation and plasticity of GABAergic synapses: Physiological mechanisms and pathophysiological implications. Pharmacology Therapeutics, 98, 299–323. PubMedCrossRef Fritschy, J.-M., & Brunig, I. (2003). Formation and plasticity of GABAergic synapses: Physiological mechanisms and pathophysiological implications. Pharmacology Therapeutics, 98, 299–323. PubMedCrossRef
go back to reference Geary, W. A., & Wooten, G. F. (1983). Quantitative film autoradiography of opiate agonist and antagonist binding in rat brain. Journal of Pharmacology and Experimental Therapeutics, 225, 234–240. PubMed Geary, W. A., & Wooten, G. F. (1983). Quantitative film autoradiography of opiate agonist and antagonist binding in rat brain. Journal of Pharmacology and Experimental Therapeutics, 225, 234–240. PubMed
go back to reference Gillberg, C., Steffenburg, S., & Jakobsson, G. (1987). Neurobiological findings in 20 relatively gifted children with Kanner-type autism or Asperger syndrome. Developmental Medicine & Child Neurology, 29, 641–649. CrossRef Gillberg, C., Steffenburg, S., & Jakobsson, G. (1987). Neurobiological findings in 20 relatively gifted children with Kanner-type autism or Asperger syndrome. Developmental Medicine & Child Neurology, 29, 641–649. CrossRef
go back to reference Goode, S., Rutter, M., & Howlin, P. (1994). A twenty year follow-up of children with autism. In 13th biennial meeting of ISSBD. Amsterdam, The Netherlands. Goode, S., Rutter, M., & Howlin, P. (1994). A twenty year follow-up of children with autism. In 13th biennial meeting of ISSBD. Amsterdam, The Netherlands.
go back to reference Houser, C. R., Miyashiro, J. E., Swartz, B. E., Walsh, G. O., Rich, J. R., & Delgado-Escueta, A. V. (1990). Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy. Journal of Neuroscience, 10, 267–282. PubMed Houser, C. R., Miyashiro, J. E., Swartz, B. E., Walsh, G. O., Rich, J. R., & Delgado-Escueta, A. V. (1990). Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy. Journal of Neuroscience, 10, 267–282. PubMed
go back to reference Kemper, T. L., & Bauman, M. L. (1998). Neuropathology of infantile autism. Journal of Neuropathology & Experimental Neurology, 57, 645–652. CrossRef Kemper, T. L., & Bauman, M. L. (1998). Neuropathology of infantile autism. Journal of Neuropathology & Experimental Neurology, 57, 645–652. CrossRef
go back to reference Lawrence, Y., Kemper, T. L., Bauman, M. L., & Blatt, G. J. (2004). Increased density of parvalbumin labeled hippocampal interneurons in autism. International Meeting for Autism Research Abstracts, 3, 45–46. Lawrence, Y., Kemper, T. L., Bauman, M. L., & Blatt, G. J. (2004). Increased density of parvalbumin labeled hippocampal interneurons in autism. International Meeting for Autism Research Abstracts, 3, 45–46.
go back to reference Matheja, P., Ludemann, P., Kuwert, T., Weckesser, M., Kellinghaus, C., Weitemeyer, L., Diehl, B., Schuierer, G., Ringelstein, E. B., & Schober, O. (2001). Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy. Journal of Neurology, 248, 585–591. PubMedCrossRef Matheja, P., Ludemann, P., Kuwert, T., Weckesser, M., Kellinghaus, C., Weitemeyer, L., Diehl, B., Schuierer, G., Ringelstein, E. B., & Schober, O. (2001). Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy. Journal of Neurology, 248, 585–591. PubMedCrossRef
go back to reference Mohler, H., Benke, B., Benson, J., Luscher, B., Rudolph, U., & Fritschy, J. M. (1997). Diversity in structure, pharmacology and regulation of GABA A receptors. In S. J. Enna, & N. G. Bowery (Eds.), The GABA receptors (pp. 11–36, Ch. 2). Totawa, NJ: Humana Press. Mohler, H., Benke, B., Benson, J., Luscher, B., Rudolph, U., & Fritschy, J. M. (1997). Diversity in structure, pharmacology and regulation of GABA A receptors. In S. J. Enna, & N. G. Bowery (Eds.), The GABA receptors (pp. 11–36, Ch. 2). Totawa, NJ: Humana Press.
go back to reference Mohler, H., Benke, D., Fritschy, J. M., & Benson, J. (2000). The benzodiazepine site of GABA A receptors. In D. L. Martin, & R. W. Olsen (Eds.), GABA in the nervous system: The view at fifty years (pp. 97–112, Ch. 7). Philadelphia: Lippincott Williams and Wilkins. Mohler, H., Benke, D., Fritschy, J. M., & Benson, J. (2000). The benzodiazepine site of GABA A receptors. In D. L. Martin, & R. W. Olsen (Eds.), GABA in the nervous system: The view at fifty years (pp. 97–112, Ch. 7). Philadelphia: Lippincott Williams and Wilkins.
go back to reference Mohler, H., Fritschy, J. M., Crestani, F., Hensch, T., & Rudolph, U. (2004). Specific GABA A circuits in brain development and therapy. Biochemical Pharmacology, 68, 1685–1690. PubMedCrossRef Mohler, H., Fritschy, J. M., Crestani, F., Hensch, T., & Rudolph, U. (2004). Specific GABA A circuits in brain development and therapy. Biochemical Pharmacology, 68, 1685–1690. PubMedCrossRef
go back to reference Nurmi, E. L., Dowd, M., Tadevosyan-Leyfer, O., Haines, J. L., Folstein, S. E., & Sutcliffe, J. S. (2003). Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13. Journal of American Academy of Adolescent Psychiatry, 42, 856–863. CrossRef Nurmi, E. L., Dowd, M., Tadevosyan-Leyfer, O., Haines, J. L., Folstein, S. E., & Sutcliffe, J. S. (2003). Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13. Journal of American Academy of Adolescent Psychiatry, 42, 856–863. CrossRef
go back to reference Olsson, I., Steffenburg, S., & Gillberg, C. (1988). Epilepsy in autism and autistic-like conditions: A population based study. Archives of Neurology, 45, 666–668. PubMed Olsson, I., Steffenburg, S., & Gillberg, C. (1988). Epilepsy in autism and autistic-like conditions: A population based study. Archives of Neurology, 45, 666–668. PubMed
go back to reference Raymond, G. V., Bauman, M. L., & Kemper, T. L. (1996). Hippocampus in autism: A Golgi analysis. Acta Neuropathologica, 91, 117–119. PubMedCrossRef Raymond, G. V., Bauman, M. L., & Kemper, T. L. (1996). Hippocampus in autism: A Golgi analysis. Acta Neuropathologica, 91, 117–119. PubMedCrossRef
go back to reference Ritvo, E. R., Freeman, B. J., Scheibel, A. B., Duong, T., Robinson, H., Guthrie, D., & Ritvo, A. (1986). Lower Purkinje cell counts in the cerebella of four autistic subjects: Initial findings of the UCLA-NSAC autopsy research report. American Journal of Psychiatry, 146, 862–866. Ritvo, E. R., Freeman, B. J., Scheibel, A. B., Duong, T., Robinson, H., Guthrie, D., & Ritvo, A. (1986). Lower Purkinje cell counts in the cerebella of four autistic subjects: Initial findings of the UCLA-NSAC autopsy research report. American Journal of Psychiatry, 146, 862–866.
go back to reference Rosene, D. L., & Van Hoesen, G. W. (1987). The hippocampal formation of the primate brain: A review of some comparative aspects of cytoarchitecture and connections. In E. G. Jones, & A. Peters (Eds.), Cerebral cortex (Vol. 6, pp. 345–456). New York: Plenum Press. Rosene, D. L., & Van Hoesen, G. W. (1987). The hippocampal formation of the primate brain: A review of some comparative aspects of cytoarchitecture and connections. In E. G. Jones, & A. Peters (Eds.), Cerebral cortex (Vol. 6, pp. 345–456). New York: Plenum Press.
go back to reference Rutter, M. (1970). Autistic children: Infancy to adulthood. Seminars in Psychiatry, 2, 435–450. PubMed Rutter, M. (1970). Autistic children: Infancy to adulthood. Seminars in Psychiatry, 2, 435–450. PubMed
go back to reference Savic, I., Persson, A., & Roland, P. (1988). In vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci. Lancet, 2, 863–866. PubMedCrossRef Savic, I., Persson, A., & Roland, P. (1988). In vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci. Lancet, 2, 863–866. PubMedCrossRef
go back to reference Schroer, R. J., Phelan, M. C., Michaelis, R. C., Crawford, E. C., Skinner, S. A., Cuccaro, M., Simensen, R. J., Bishop, J., Skinner, C., Fender, D., & Stevenson, R. E. (1998). Autism and maternally derived aberrations of chromosome 15q. American Journal of Medical Genetics, 76, 327–336. PubMedCrossRef Schroer, R. J., Phelan, M. C., Michaelis, R. C., Crawford, E. C., Skinner, S. A., Cuccaro, M., Simensen, R. J., Bishop, J., Skinner, C., Fender, D., & Stevenson, R. E. (1998). Autism and maternally derived aberrations of chromosome 15q. American Journal of Medical Genetics, 76, 327–336. PubMedCrossRef
go back to reference Shao, Y., Cuccaro, M. L., Hauser, E. R., Raiford, K. L., Menold, M. M., Wolpert, C. M., Ravan, S. A., Elston, L., Decena, K., Donnelly, S. L., Abramson, R. K., Wright, H. H., DeLong, G. R., Golbert, J. R., & Pericak-Vance, M. A. (2003). Fine mapping of autistic disorder to chromosome 15q11-q13 by use of phenotypic subtypes. American Journal of Human Genetics, 72, 539–548. PubMedCrossRef Shao, Y., Cuccaro, M. L., Hauser, E. R., Raiford, K. L., Menold, M. M., Wolpert, C. M., Ravan, S. A., Elston, L., Decena, K., Donnelly, S. L., Abramson, R. K., Wright, H. H., DeLong, G. R., Golbert, J. R., & Pericak-Vance, M. A. (2003). Fine mapping of autistic disorder to chromosome 15q11-q13 by use of phenotypic subtypes. American Journal of Human Genetics, 72, 539–548. PubMedCrossRef
go back to reference Shaw, C., Aoki, C., Wilkinson, M., Prusky, G., & Cynader, M. (1987). Benzodiazepine ([ 3H]flunitrazepam) binding in cat visual cortex: Ontogenesis of normal characteristics and the effects of dark rearing. Developmental Brain Research, 37, 67–76. CrossRef Shaw, C., Aoki, C., Wilkinson, M., Prusky, G., & Cynader, M. (1987). Benzodiazepine ([ 3H]flunitrazepam) binding in cat visual cortex: Ontogenesis of normal characteristics and the effects of dark rearing. Developmental Brain Research, 37, 67–76. CrossRef
go back to reference Volkmar, F. R., & Nelson, I. (1990). Seizure disorders in autism. Journal of the American Academy of Adolescent Psychiatry, 29, 127–129. CrossRef Volkmar, F. R., & Nelson, I. (1990). Seizure disorders in autism. Journal of the American Academy of Adolescent Psychiatry, 29, 127–129. CrossRef
go back to reference Werck, M. C., & Daval, J. L. (1991). Autoradiographic changes in central benzodiazepine binding sites and their coupling to gama-aminobutyric acid receptors after seizures in the developing rat. Pediatric Research, 30, 100–105. PubMed Werck, M. C., & Daval, J. L. (1991). Autoradiographic changes in central benzodiazepine binding sites and their coupling to gama-aminobutyric acid receptors after seizures in the developing rat. Pediatric Research, 30, 100–105. PubMed
go back to reference Whitney, E. R., Kemper, T. L., Bauman, M. L., & Blatt, G. J. (2004). Calbindin D-28K is a reliable marker for cerebellar Purkinje cells in control and autistic cerebellum . International Meeting for Autism Research (IMFAR) abstract, 3, 153. Whitney, E. R., Kemper, T. L., Bauman, M. L., & Blatt, G. J. (2004). Calbindin D-28K is a reliable marker for cerebellar Purkinje cells in control and autistic cerebellum . International Meeting for Autism Research (IMFAR) abstract, 3, 153.
go back to reference Yip, J., Soghomonian, J.-J., Nguyen, L. T., & Blatt, G. J. (2005). Decreased GAD67 in Purkinje cells in the posterolateral cerebellar cortex in autism: An in situ hybrization study. Society for Neuroscience abstract, 35, 603.8. Yip, J., Soghomonian, J.-J., Nguyen, L. T., & Blatt, G. J. (2005). Decreased GAD67 in Purkinje cells in the posterolateral cerebellar cortex in autism: An in situ hybrization study. Society for Neuroscience abstract, 35, 603.8.
Metagegevens
Titel
[3H]-Flunitrazepam-labeled Benzodiazepine Binding Sites in the Hippocampal Formation in Autism: A Multiple Concentration Autoradiographic Study
Auteurs
Jeffrey T. Guptill
Anne B. Booker
Terrell T. Gibbs
Thomas L. Kemper
Margaret L. Bauman
Gene J. Blatt
Publicatiedatum
01-05-2007
Gepubliceerd in
Journal of Autism and Developmental Disorders / Uitgave 5/2007
Print ISSN: 0162-3257
Elektronisch ISSN: 1573-3432
DOI
https://doi.org/10.1007/s10803-006-0226-7