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Validating γ Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism

Gandal, Michael J ; Edgar, J. Christopher ; Ehrlichman, Richard S ; Mehta, Mili ; Roberts, Timothy P.L ; Siegel, Steven J

Biological psychiatry (1969), 2010-12, Vol.68 (12), p.1100-1106 [Periódico revisado por pares]

New York, NY: Elsevier Inc

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Título:
Validating γ Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism
Autor: Gandal, Michael J ; Edgar, J. Christopher ; Ehrlichman, Richard S ; Mehta, Mili ; Roberts, Timothy P.L ; Siegel, Steven J
Assuntos: Animal model ; Animals ; Animals, Newborn ; Auditory Perception - physiology ; autism ; Autistic Disorder - physiopathology ; Behavior, Animal - drug effects ; Behavior, Animal - physiology ; Biological and medical sciences ; Biomarkers ; Brain Waves - physiology ; Cell Adhesion Molecules, Neuronal - biosynthesis ; Cerebral Cortex - physiopathology ; Child ; Child clinical studies ; Developmental disorders ; Disease Models, Animal ; electrophysiology ; endophenotype ; Endophenotypes ; Evoked Potentials, Auditory - genetics ; Evoked Potentials, Auditory - physiology ; Female ; Humans ; Infantile autism ; magnetoencephalography (MEG) ; Magnetoencephalography - methods ; Male ; Medical sciences ; Membrane Proteins - biosynthesis ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins - biosynthesis ; Pregnancy ; Prenatal Exposure Delayed Effects - physiopathology ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Pyridines - pharmacology ; Temporal Lobe - physiopathology ; Valproic Acid - adverse effects ; Valproic Acid - antagonists & inhibitors ; γ oscillations
É parte de: Biological psychiatry (1969), 2010-12, Vol.68 (12), p.1100-1106
Descrição: Background Difficulty modeling complex behavioral phenotypes in rodents (e.g., language) has hindered pathophysiological investigation and treatment development for autism spectrum disorders. Recent human neuroimaging studies, however, have identified functional biomarkers that can be more directly related to the abnormal neural dynamics of autism spectrum disorders. This study assessed the translational potential of auditory evoked-response endophenotypes of autism in parallel mouse and human studies of autism. Methods Whole-cortex magnetoencephalography was recorded in 17 typically developing and 25 autistic children during auditory pure-tone presentation. Superior temporal gyrus activity was analyzed in time and frequency domains. Auditory evoked potentials were recorded in mice prenatally exposed to valproic acid (VPA) and analyzed with analogous methods. Results The VPA-exposed mice demonstrated selective behavioral alterations related to autism, including reduced social interactions and ultrasonic vocalizations, increased repetitive self-grooming, and prepulse inhibition deficits. Autistic subjects and VPA-exposed mice showed a similar 10% latency delay in the N1/M100 evoked response and a reduction in γ frequency (30–50 Hz) phase-locking factor. Electrophysiological measures were associated with mouse behavioral deficits. In mice, γ phase-locking factor was correlated with expression of the autism risk gene neuroligin-3 and neural deficits were modulated by the mGluR5-receptor antagonist MPEP. Conclusions Results demonstrate a novel preclinical approach toward mechanistic understanding and treatment development for autism.
Editor: New York, NY: Elsevier Inc
Idioma: Inglês

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Validating γ Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism

Gandal, Michael J ; Edgar, J. Christopher ; Ehrlichman, Richard S ; Mehta, Mili ; Roberts, Timothy P.L ; Siegel, Steven J

New York, NY: Elsevier Inc

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