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 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] / 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 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 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] / 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)  

Public ISBD [article]  inAutism Research > 10-11 (November 2017) . - p.1787-1796 Titre : Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism Type de document : texte imprimé Auteurs : Jean-Jacques SOGHOMONIAN, Auteur ; Kunzhong ZHANG, Auteur ; Sujithra REPRAKASH, Auteur ; Gene J. BLATT, Auteur Article en page(s) : p.1787-1796 Langues : Anglais (eng) Mots-clés : post-mortem  parvalbumin  cerebellum  GABA  gene expression Index. décimale : PER Périodiques Résumé : Recent neuropathology studies in human brains indicate that several areas of the prefrontal cortex have decreased numbers of parvalbumin interneurons or decreased parvalbumin expression in Autism Spectrum disorders (ASD) [Hashemi, Ariza, Rogers, Noctor, & Martinez-Cerdeno, 2017; Zikopoulos & Barbas, ]. These data suggest that a deficit in parvalbumin may be a key neuropathology of ASD and contribute to altered GABAergic inhibition. However, it is unclear if a deficit in parvalbumin is a phenomenon that occurs in regions other than the cerebral cortex. The cerebellum is a major region where neuropathology was first detected in ASD over three decades ago [Bauman & Kemper, ]. In view of the documented association between parvalbumin-expressing neurons and autism, the objective of the present study was to determine if parvalbumin gene expression is also altered in Purkinje neurons of the cerebellum. Radioisotopic in situ hybridization histochemistry was used on human tissue sections from control and ASD brains in order to detect and measure parvalbumin mRNA levels at the single cell level in Purkinje cells of Crus II of the lateral cerebellar hemispheres. Results indicate that parvalbumin mRNA levels are significantly lower in Purkinje cells in ASD compared to control brains. This decrease was not influenced by post-mortem interval or age at death. This result indicates that decreased parvalbumin expression is a more widespread feature of ASD. We discuss how this decrease may be implicated in altered cerebellar output to the cerebral cortex and in key ASD symptoms. Autism Res 2017, 10: 1787–1796. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The cerebellum of the brain controls movement and cognition, including memory and language. This study investigated mechanisms of cerebellar function in Autism. Our hypothesis is that parvalbumin, a molecule that controls and coordinate many cellular brain functions, contributes to the excitatory/inhibitory imbalance in Autism. We report that parvalbumin expression is depressed in Purkinje cells of the cerebellum in autism. This finding contributes to elucidate the cellular and molecular underpinings of autism and should provide a direction for future therapies. En ligne : http://dx.doi.org/10.1002/aur.1835 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322 [article] Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism [texte imprimé] / Jean-Jacques SOGHOMONIAN, Auteur ; Kunzhong ZHANG, Auteur ; Sujithra REPRAKASH, Auteur ; Gene J. BLATT, Auteur . - p.1787-1796. Langues : Anglais (eng) in Autism Research > 10-11 (November 2017) . - p.1787-1796 Mots-clés : post-mortem  parvalbumin  cerebellum  GABA  gene expression Index. décimale : PER Périodiques Résumé : Recent neuropathology studies in human brains indicate that several areas of the prefrontal cortex have decreased numbers of parvalbumin interneurons or decreased parvalbumin expression in Autism Spectrum disorders (ASD) [Hashemi, Ariza, Rogers, Noctor, & Martinez-Cerdeno, 2017; Zikopoulos & Barbas, ]. These data suggest that a deficit in parvalbumin may be a key neuropathology of ASD and contribute to altered GABAergic inhibition. However, it is unclear if a deficit in parvalbumin is a phenomenon that occurs in regions other than the cerebral cortex. The cerebellum is a major region where neuropathology was first detected in ASD over three decades ago [Bauman & Kemper, ]. In view of the documented association between parvalbumin-expressing neurons and autism, the objective of the present study was to determine if parvalbumin gene expression is also altered in Purkinje neurons of the cerebellum. Radioisotopic in situ hybridization histochemistry was used on human tissue sections from control and ASD brains in order to detect and measure parvalbumin mRNA levels at the single cell level in Purkinje cells of Crus II of the lateral cerebellar hemispheres. Results indicate that parvalbumin mRNA levels are significantly lower in Purkinje cells in ASD compared to control brains. This decrease was not influenced by post-mortem interval or age at death. This result indicates that decreased parvalbumin expression is a more widespread feature of ASD. We discuss how this decrease may be implicated in altered cerebellar output to the cerebral cortex and in key ASD symptoms. Autism Res 2017, 10: 1787–1796. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The cerebellum of the brain controls movement and cognition, including memory and language. This study investigated mechanisms of cerebellar function in Autism. Our hypothesis is that parvalbumin, a molecule that controls and coordinate many cellular brain functions, contributes to the excitatory/inhibitory imbalance in Autism. We report that parvalbumin expression is depressed in Purkinje cells of the cerebellum in autism. This finding contributes to elucidate the cellular and molecular underpinings of autism and should provide a direction for future therapies. En ligne : http://dx.doi.org/10.1002/aur.1835 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322

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

Public ISBD contenu dans The Neurochemical Basis of Autism / Gene J. BLATT Titre : Glutamic Acid Decarboxylase (GAD) as a Biomarker of GABAergic Activity in Autism: Impact on Cerebellar Circuitry and Function Type de document : texte imprimé Auteurs : Gene J. BLATT, Auteur ; Jean-Jacques SOGHOMONIAN, Auteur ; Jane YIP, Auteur Année de publication : 2010 Importance : p.95-111 Langues : Anglais (eng) Mots-clés : Glutamate Decarboxylase  Acide ?-aminobutyrique Index. décimale : SCI-D SCI-D - Neurosciences Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=109 contenu dans The Neurochemical Basis of Autism / Gene J. BLATT Glutamic Acid Decarboxylase (GAD) as a Biomarker of GABAergic Activity in Autism: Impact on Cerebellar Circuitry and Function [texte imprimé] / Gene J. BLATT, Auteur ; Jean-Jacques SOGHOMONIAN, Auteur ; Jane YIP, Auteur . - 2010 . - p.95-111. Langues : Anglais (eng) Mots-clés : Glutamate Decarboxylase  Acide ?-aminobutyrique Index. décimale : SCI-D SCI-D - Neurosciences Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=109

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