[3H]-Flunitrazepam-labeled Benzodiazepine Binding Sites in the Hippocampal Formation in Autism: A Multiple Concentration Autoradiographic Study / Jeffrey T. GUPTILL in Journal of Autism and Developmental Disorders, 37-5 (May 2007)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 37-5 (May 2007) . - p.911-920 Titre : [3H]-Flunitrazepam-labeled Benzodiazepine Binding Sites in the Hippocampal Formation in Autism: A Multiple Concentration Autoradiographic Study Type de document : Texte imprimé et/ou numérique Auteurs : Jeffrey T. GUPTILL, Auteur ; Anne B. BOOKER, Auteur ; Terrell T. GIBBS, Auteur ; Thomas L. KEMPER, Auteur ; Gene J. BLATT, Auteur ; Margaret L. BAUMAN, Auteur Année de publication : 2007 Article en page(s) : p.911-920 Langues : Anglais (eng) Mots-clés : Developmental-disorder Autoradiography Hippocampus GABAergic-receptors Hippocampal-circuitry Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1007/s10803-006-0226-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=140 [article] [3H]-Flunitrazepam-labeled Benzodiazepine Binding Sites in the Hippocampal Formation in Autism: A Multiple Concentration Autoradiographic Study [Texte imprimé et/ou numérique] / Jeffrey T. GUPTILL, Auteur ; Anne B. BOOKER, Auteur ; Terrell T. GIBBS, Auteur ; Thomas L. KEMPER, Auteur ; Gene J. BLATT, Auteur ; Margaret L. BAUMAN, Auteur . - 2007 . - p.911-920. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 37-5 (May 2007) . - p.911-920 Mots-clés : Developmental-disorder Autoradiography Hippocampus GABAergic-receptors Hippocampal-circuitry Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1007/s10803-006-0226-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=140

Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism / Adrian L. OBLAK in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.200-211 Titre : Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism Type de document : Texte imprimé et/ou numérique Auteurs : Adrian L. OBLAK, Auteur ; Douglas L. ROSENE, Auteur ; Thomas L. KEMPER, Auteur ; Margaret L. BAUMAN, Auteur ; Gene J. BLATT, Auteur Année de publication : 2011 Article en page(s) : p.200-211 Langues : Anglais (eng) Mots-clés : neuropathology  gamma-aminobutyric acid  neurochemistry ;neuroanatomy Index. décimale : PER Périodiques Résumé : Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social-emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin-stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin-and calbindin-immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social–emotional behaviors as well as functioning of interrelated areas. En ligne : http://dx.doi.org/10.1002/aur.188 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism [Texte imprimé et/ou numérique] / Adrian L. OBLAK, Auteur ; Douglas L. ROSENE, Auteur ; Thomas L. KEMPER, Auteur ; Margaret L. BAUMAN, Auteur ; Gene J. BLATT, Auteur . - 2011 . - p.200-211. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.200-211 Mots-clés : neuropathology  gamma-aminobutyric acid  neurochemistry ;neuroanatomy Index. décimale : PER Périodiques Résumé : Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social-emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin-stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin-and calbindin-immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social–emotional behaviors as well as functioning of interrelated areas. En ligne : http://dx.doi.org/10.1002/aur.188 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

Basal ganglia and autism – a translational perspective / Krishna SUBRAMANIAN in Autism Research, 10-11 (November 2017)  

Public ISBD [article]  inAutism Research > 10-11 (November 2017) . - p.1751-1775 Titre : Basal ganglia and autism – a translational perspective Type de document : Texte imprimé et/ou numérique Auteurs : Krishna SUBRAMANIAN, Auteur ; Cheryl BRANDENBURG, Auteur ; Fernanda ORSATI, Auteur ; Jean-Jacques SOGHOMONIAN, Auteur ; John P. HUSSMAN, Auteur ; Gene J. BLATT, Auteur Article en page(s) : p.1751-1775 Langues : Anglais (eng) Mots-clés : basal ganglia  animal models  motor, autism  neuroanatomy  neuroimaging  neuropathology Index. décimale : PER Périodiques Résumé : The basal ganglia are a collection of nuclei below the cortical surface that are involved in both motor and non-motor functions, including higher order cognition, social interactions, speech, and repetitive behaviors. Motor development milestones that are delayed in autism such as gross motor, fine motor and walking can aid in early diagnosis of autism. Neuropathology and neuroimaging findings in autism cases revealed volumetric changes and altered cell density in select basal ganglia nuclei. Interestingly, in autism, both the basal ganglia and the cerebellum are impacted both in their motor and non-motor domains and recently, found to be connected via the pons through a short disynaptic pathway. In typically developing individuals, the basal ganglia plays an important role in: eye movement, movement coordination, sensory modulation and processing, eye-hand coordination, action chaining, and inhibition control. Genetic models have proved to be useful toward understanding cellular and molecular changes at the synaptic level in the basal ganglia that may in part contribute to these autism-related behaviors. In autism, basal ganglia functions in motor skill acquisition and development are altered, thus disrupting the normal flow of feedback to the cortex. Taken together, there is an abundance of emerging evidence that the basal ganglia likely plays critical roles in maintaining an inhibitory balance between cortical and subcortical structures, critical for normal motor actions and cognitive functions. In autism, this inhibitory balance is disturbed thus impacting key pathways that affect normal cortical network activity. Autism Res 2017, 10: 1751–1775. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Habit learning, action selection and performance are modulated by the basal ganglia, a collection of groups of neurons located below the cerebral cortex in the brain. In autism, there is emerging evidence that parts of the basal ganglia are structurally and functionally altered disrupting normal information flow. The basal ganglia through its interconnected circuits with the cerebral cortex and the cerebellum can potentially impact various motor and cognitive functions in the autism brain. En ligne : http://dx.doi.org/10.1002/aur.1837 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322 [article] Basal ganglia and autism – a translational perspective [Texte imprimé et/ou numérique] / Krishna SUBRAMANIAN, Auteur ; Cheryl BRANDENBURG, Auteur ; Fernanda ORSATI, Auteur ; Jean-Jacques SOGHOMONIAN, Auteur ; John P. HUSSMAN, Auteur ; Gene J. BLATT, Auteur . - p.1751-1775. Langues : Anglais (eng) in Autism Research > 10-11 (November 2017) . - p.1751-1775 Mots-clés : basal ganglia  animal models  motor, autism  neuroanatomy  neuroimaging  neuropathology Index. décimale : PER Périodiques Résumé : The basal ganglia are a collection of nuclei below the cortical surface that are involved in both motor and non-motor functions, including higher order cognition, social interactions, speech, and repetitive behaviors. Motor development milestones that are delayed in autism such as gross motor, fine motor and walking can aid in early diagnosis of autism. Neuropathology and neuroimaging findings in autism cases revealed volumetric changes and altered cell density in select basal ganglia nuclei. Interestingly, in autism, both the basal ganglia and the cerebellum are impacted both in their motor and non-motor domains and recently, found to be connected via the pons through a short disynaptic pathway. In typically developing individuals, the basal ganglia plays an important role in: eye movement, movement coordination, sensory modulation and processing, eye-hand coordination, action chaining, and inhibition control. Genetic models have proved to be useful toward understanding cellular and molecular changes at the synaptic level in the basal ganglia that may in part contribute to these autism-related behaviors. In autism, basal ganglia functions in motor skill acquisition and development are altered, thus disrupting the normal flow of feedback to the cortex. Taken together, there is an abundance of emerging evidence that the basal ganglia likely plays critical roles in maintaining an inhibitory balance between cortical and subcortical structures, critical for normal motor actions and cognitive functions. In autism, this inhibitory balance is disturbed thus impacting key pathways that affect normal cortical network activity. Autism Res 2017, 10: 1751–1775. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Habit learning, action selection and performance are modulated by the basal ganglia, a collection of groups of neurons located below the cerebral cortex in the brain. In autism, there is emerging evidence that parts of the basal ganglia are structurally and functionally altered disrupting normal information flow. The basal ganglia through its interconnected circuits with the cerebral cortex and the cerebellum can potentially impact various motor and cognitive functions in the autism brain. En ligne : http://dx.doi.org/10.1002/aur.1837 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322

Decreased GABA A receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism / Adrian L. OBLAK in Autism Research, 2-4 (August 2009)  

Public ISBD [article]  inAutism Research > 2-4 (August 2009) . - p.205-219 Titre : Decreased GABA A receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism Type de document : Texte imprimé et/ou numérique Auteurs : Adrian L. OBLAK, Auteur ; Terrell T. GIBBS, Auteur ; Gene J. BLATT, Auteur Année de publication : 2009 Article en page(s) : p.205-219 Langues : Anglais (eng) Mots-clés : autistic anterior-cingulate-cortex GABA post-mortem ligand-binding Index. décimale : PER Périodiques Résumé : The anterior cingulate cortex (ACC; BA 24) via its extensive limbic and high order association cortical connectivity to prefrontal cortex is a key part of an important circuitry participating in executive function, affect, and socio-emotional behavior. Multiple lines of evidence, including genetic and imaging studies, suggest that the ACC and gamma-amino-butyric acid (GABA) system may be affected in autism. The benzodiazepine binding site on the GABAA receptor complex is an important target for pharmacotherapy and has important clinical implications. The present multiple-concentration ligand-binding study utilized 3H-muscimol and 3H-flunitrazepam to determine the number (Bmax), binding affinity (Kd), and distribution of GABAA receptors and benzodiazepine binding sites, respectively, in the ACC in adult autistic and control cases. Compared to controls, the autistic group had significant decreases in the mean density of GABAA receptors in the supragranular (46.8%) and infragranular (20.2%) layers of the ACC and in the density of benzodiazepine binding sites in the supragranular (28.9%) and infragranular (16.4%) lamina. In addition, a trend for a decrease in for the density of benzodiazepine sites was found in the infragranular layers (17.1%) in the autism group. These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABAA receptors in the ACC may be the result of increased GABA innervation and/or release disturbing the delicate excitation/inhibition balance of principal neurons as well as their output to key limbic cortical targets. Such disturbances likely underlie the core alterations in socio-emotional behaviors in autism. En ligne : http://dx.doi.org/10.1002/aur.88 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=937 [article] Decreased GABA A receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism [Texte imprimé et/ou numérique] / Adrian L. OBLAK, Auteur ; Terrell T. GIBBS, Auteur ; Gene J. BLATT, Auteur . - 2009 . - p.205-219. Langues : Anglais (eng) in Autism Research > 2-4 (August 2009) . - p.205-219 Mots-clés : autistic anterior-cingulate-cortex GABA post-mortem ligand-binding Index. décimale : PER Périodiques Résumé : The anterior cingulate cortex (ACC; BA 24) via its extensive limbic and high order association cortical connectivity to prefrontal cortex is a key part of an important circuitry participating in executive function, affect, and socio-emotional behavior. Multiple lines of evidence, including genetic and imaging studies, suggest that the ACC and gamma-amino-butyric acid (GABA) system may be affected in autism. The benzodiazepine binding site on the GABAA receptor complex is an important target for pharmacotherapy and has important clinical implications. The present multiple-concentration ligand-binding study utilized 3H-muscimol and 3H-flunitrazepam to determine the number (Bmax), binding affinity (Kd), and distribution of GABAA receptors and benzodiazepine binding sites, respectively, in the ACC in adult autistic and control cases. Compared to controls, the autistic group had significant decreases in the mean density of GABAA receptors in the supragranular (46.8%) and infragranular (20.2%) layers of the ACC and in the density of benzodiazepine binding sites in the supragranular (28.9%) and infragranular (16.4%) lamina. In addition, a trend for a decrease in for the density of benzodiazepine sites was found in the infragranular layers (17.1%) in the autism group. These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABAA receptors in the ACC may be the result of increased GABA innervation and/or release disturbing the delicate excitation/inhibition balance of principal neurons as well as their output to key limbic cortical targets. Such disturbances likely underlie the core alterations in socio-emotional behaviors in autism. En ligne : http://dx.doi.org/10.1002/aur.88 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=937

Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study / Jane YIP in Autism Research, 2-1 (February 2009)  

Public ISBD [article]  inAutism Research > 2-1 (February 2009) . - p.50-59 Titre : Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study Type de document : Texte imprimé et/ou numérique Auteurs : Jane YIP, Auteur ; Gene J. BLATT, Auteur ; Jean Jacques SOGHOMONIAN, Auteur Année de publication : 2009 Article en page(s) : p.50-59 Langues : Anglais (eng) Mots-clés : dentate-nucleus cerebellum autistic GABA dysregulation cerebellar-nuclei Index. décimale : PER Périodiques Résumé : The laterally positioned dentate nuclei lie in a key position in the cerebellum to receive input from Purkinje cells in the lateral cerebellar hemisphere participating in both motor and cognitive functions. Although neuropathology of the four cerebellar nuclei using Nissl staining has been qualitatively reported in children and adults with autism, surprisingly the dentate nuclei appeared less affected despite reported reductions in Purkinje cells in the posterolateral cerebellar hemisphere. To determine any underlying abnormalities in the critically important GABAergic system, the rate-limiting GABA synthesizing enzyme, glutamic acid decarboxylase (GAD) type 65 was measured via in situ hybridization histochemistry in dentate somata. GAD65 mRNA labeling revealed two distinct subpopulations of neurons in adult control and autism postmortem brains: small-sized cells (about 10-12 µm in diameter, presumed interneurons) and larger-sized neurons (about 18-20 µm in diameter, likely feedback to inferior olivary neurons). A mean 51% reduction in GAD65 mRNA levels was found in the larger labeled cells in the autistic group compared with the control group (P=0.009; independent t-test) but not in the smaller cell subpopulation. This suggests a disturbance in the intrinsic cerebellar circuitry in the autism group potentially interfering with the synchronous firing of inferior olivary neurons, and the timing of Purkinje cell firing and inputs to the dentate nuclei. Disturbances in critical neural substrates within these key circuits could disrupt afferents to motor and/or cognitive cerebral association areas in the autistic brain likely contributing to the marked behavioral consequences characteristic of autism. En ligne : http://dx.doi.org/10.1002/aur.62 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=935 [article] Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization study [Texte imprimé et/ou numérique] / Jane YIP, Auteur ; Gene J. BLATT, Auteur ; Jean Jacques SOGHOMONIAN, Auteur . - 2009 . - p.50-59. Langues : Anglais (eng) in Autism Research > 2-1 (February 2009) . - p.50-59 Mots-clés : dentate-nucleus cerebellum autistic GABA dysregulation cerebellar-nuclei Index. décimale : PER Périodiques Résumé : The laterally positioned dentate nuclei lie in a key position in the cerebellum to receive input from Purkinje cells in the lateral cerebellar hemisphere participating in both motor and cognitive functions. Although neuropathology of the four cerebellar nuclei using Nissl staining has been qualitatively reported in children and adults with autism, surprisingly the dentate nuclei appeared less affected despite reported reductions in Purkinje cells in the posterolateral cerebellar hemisphere. To determine any underlying abnormalities in the critically important GABAergic system, the rate-limiting GABA synthesizing enzyme, glutamic acid decarboxylase (GAD) type 65 was measured via in situ hybridization histochemistry in dentate somata. GAD65 mRNA labeling revealed two distinct subpopulations of neurons in adult control and autism postmortem brains: small-sized cells (about 10-12 µm in diameter, presumed interneurons) and larger-sized neurons (about 18-20 µm in diameter, likely feedback to inferior olivary neurons). A mean 51% reduction in GAD65 mRNA levels was found in the larger labeled cells in the autistic group compared with the control group (P=0.009; independent t-test) but not in the smaller cell subpopulation. This suggests a disturbance in the intrinsic cerebellar circuitry in the autism group potentially interfering with the synchronous firing of inferior olivary neurons, and the timing of Purkinje cell firing and inputs to the dentate nuclei. Disturbances in critical neural substrates within these key circuits could disrupt afferents to motor and/or cognitive cerebral association areas in the autistic brain likely contributing to the marked behavioral consequences characteristic of autism. En ligne : http://dx.doi.org/10.1002/aur.62 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=935

Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism / Jean-Jacques SOGHOMONIAN in Autism Research, 10-11 (November 2017)  

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GABAergic cerebellar system in autism : a neuropathological and developmental perspective / Gene J. BLATT

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Gaps in Current Autism Research: The Thoughts of the Autism Research Editorial Board and Associate Editors / David G. AMARAL in Autism Research, 12-5 (May 2019)  

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Glutamic Acid Decarboxylase (GAD) as a Biomarker of GABAergic Activity in Autism: Impact on Cerebellar Circuitry and Function / Gene J. BLATT

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Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies / Andre W. PHILLIPS ; Elena ARTIMOVICH ; Jonathan E. NESTOR ; John P. HUSSMAN ; Gene J. BLATT in Autism Research, 9-5 (May 2016)  

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Inhibitory and Excitatory Systems in Autism Spectrum Disorders / Gene J. BLATT

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Reduced Serotonin Receptor Subtypes in a Limbic and a Neocortical Region in Autism / Adrian OBLAK in Autism Research, 6-6 (December 2013)  

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The GABAergic system in autism / Gene J. BLATT

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The Neurochemical Basis of Autism / Gene J. BLATT

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