Deep brain stimulation modified autism-like deficits via the serotonin system in a valproic acid-induced rat model

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题名:	Deep brain stimulation modified autism-like deficits via the serotonin system in a valproic acid-induced rat model
作者:	Wu, Han-Fang;Chen, Yi-Ju;Chu, Ming-Chia;Hsu, Ya-Ting;Lu, Ting-Yi;Chen, I-Tuan;Chen, Po See;Lin, Hui-Ching
贡献者:	視光學系
关键词:	deep brain stimulation;autism spectrum disorder;valproic acid;serotonin system
日期:	2018-09-01
上传时间:	2025-08-11 14:43:58 (UTC+8)
摘要:	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 expressions of NR2B subunit of N-methyl-D-aspartate receptors (NMDARs) and the β3 subunit of γ-aminobutyric acid type A receptors (GABAAR) in the PFC region. These results provided the first evidence of characteristic behavioral changes in VPA-induced offspring caused by DBS via the 5-HT system in the ILPFC.
關聯:	International Journal of Molecular Sciences, 19(9). https://doi.org/10.3390/ijms19092840
显示于类别:	[視光學系] 期刊論文

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