Deep Brain Stimulation Modified Autism-Like Deficits via the Serotonin System in a Valproic Acid-Induced Rat Model

International Journal of Molecular Sciences
Han-Fang WuHui-Ching Lin

Abstract

Deep brain stimulation (DBS) is known to be a promising treatment for resistant depression, which acts via the serotonin (5-hydroxytryptamine, 5-HT) system in the infralimbic prefrontal cortex (ILPFC). Previous study revealed that dysfunction of brain 5-HT homeostasis is related to a valproate (VPA)-induced rat autism spectrum disorder (ASD) model. Whether ILPFC DBS rescues deficits in VPA-induced offspring through the 5-HT system is not known. Using VPA-induced offspring, we therefore explored the effect of DBS in autistic phenotypes and further investigated the underlying mechanism. Using combined behavioral and molecular approaches, we observed that applying DBS and 5-HT1A receptor agonist treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reversed sociability deficits, anxiety and hyperactivity in the VPA-exposed offspring. We then administered the selective 5-HT1A receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate (WAY 100635), following which the effect of DBS in terms of improving autistic behaviors was blocked in the VPA-exposed offspring. Furthermore, we found that both 8-OH-DPAT and DBS treatment rescued autistic behaviors by decreasing the exp...Continue Reading

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Citations

Jan 10, 2021·NeuroImage. Clinical·A Cárdenas-de-la-ParraUNKNOWN IBIS Network
Jun 12, 2021·Journal of Autism and Developmental Disorders·William E DeCoteau, Adam E Fox
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jieon LeeHyunah Choo
Aug 19, 2020·Developmental Neuroscience·Devahuti ChalihaJohn Mamo

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Methods Mentioned

BETA
electrophoresis

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