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http://140.112.115.32:8080/ir/handle/987654321/2794
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| Title: | Deep brain stimulation modified autism-like deficits via the serotonin system in a valproic acid-induced rat model |
| Authors: | Han-Fang Wu;Yi-Ju Chen;Ming-Chia Chu;Ya-Ting Hsu;Ting-Yi Lu;I-Tuan Chen;Po See Chen;Hui-Ching Lin |
| Contributors: | 視光學系 |
| Keywords: | deep brain stimulation;autism spectrum disorder;valproic acid;serotonin system |
| Date: | 2018-09-01 |
| Issue Date: | 2025-08-11 14:43:58 (UTC+8) |
| 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 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. |
| Relation: | International Journal of Molecular Sciences, 19(9). https://doi.org/10.3390/ijms19092840 |
| Appears in Collections: | [視光學系] 期刊論文
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