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• W4361216790 endingPage "166700" @default.
• W4361216790 startingPage "166700" @default.
• W4361216790 abstract "Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder. Abnormal pain sensation is a common clinical symptom of ASD that seriously affects the quality of life of patients with ASD and their families. However, the underlying mechanism is unclear. It is believed to be related to the excitability of neurons and the expression of ion channels. Herein, we confirmed that baseline pain and Complete Freund's adjuvant (CFA)-induced chronic inflammatory pain were impaired in the BTBR T+ Itpr3tf/J (BTBR) mouse model of ASD. RNA sequencing (RNA-seq) analyses of the dorsal root ganglia (DRG), which are closely related to pain in ASD model mice, revealed that high expression of KCNJ10 (encoding Kir4.1) might be an important factor in ASD pain sensation abnormalities. The levels of Kir4.1 were further verified by western blotting, RT-qPCR, and immunofluorescence. By inhibiting Kir4.1, the pain insensitivity of BTBR mice improved, confirming that a high expression level of Kir4.1 was highly correlated with decreased pain sensitivity in ASD. Meanwhile, we found that the anxiety behaviours and the social novelty recognition were changed after CFA induced inflammatory pain. And after inhibiting Kir4.1, the stereotyped behaviours and social novelty recognition of BTBR mice were also improved. Further, we found that the expression levels of glutamate transporters, excitatory amino acid transporter 1 (EAAT1), and excitatory amino acid transporter 2 (EAAT2) were increased in the DRG of BTBR mice but decreased after inhibiting Kir4.1. This suggests that Kir4.1 may play a key role in the improvement of pain insensitivity in ASD by regulating glutamate transporters. In conclusion, our findings revealed the possible mechanism and role of Kir4.1 in the pain insensitivity in ASD, using bioinformatics analyses and animal experiments, and provided a theoretical basis for clinically targeted intervention in ASD." @default.
• W4361216790 created "2023-03-31" @default.
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• W4361216790 date "2023-06-01" @default.
• W4361216790 modified "2023-10-15" @default.
• W4361216790 title "Involvement of Kir4.1 in pain insensitivity of the BTBR mouse model of autism spectrum disorder" @default.
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• W4361216790 doi "https://doi.org/10.1016/j.bbadis.2023.166700" @default.
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• W4361216790 hasPublicationYear "2023" @default.
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