Biological psychiatry · 2010
Validating γ oscillations and delayed auditory responses as translational biomarkers of autism.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАВалидационное исследованиеНазвание и аннотация: Перевод в очереди
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Gandal Michael J, Edgar J Christopher, Ehrlichman Richard S, Mehta Mili, Roberts Timothy P L, Siegel Steven J
Аннотация
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.
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.
Предметные рубрики MeSH
AnimalsAnimals, NewbornAuditory PerceptionAutistic DisorderBehavior, AnimalBiomarkersBrain WavesCell Adhesion Molecules, NeuronalCerebral CortexChildDisease Models, AnimalEndophenotypesEvoked Potentials, AuditoryFemaleHumansMagnetoencephalographyMaleMembrane ProteinsMiceMice, Inbred C57BLNerve Tissue ProteinsPregnancyPrenatal Exposure Delayed EffectsPyridinesTemporal LobeValproic Acid