PMID- 36990129
OWN - NLM
STAT- MEDLINE
DCOM- 20230508
LR  - 20230825
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1869
IP  - 5
DP  - 2023 Jun
TI  - Involvement of Kir4.1 in pain insensitivity of the BTBR mouse model of autism 
      spectrum disorder.
PG  - 166700
LID - S0925-4439(23)00066-2 [pii]
LID - 10.1016/j.bbadis.2023.166700 [doi]
AB  - 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.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Li, Xiang
AU  - Li X
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Li, Qi
AU  - Li Q
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Xu, Lisha
AU  - Xu L
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Ma, Zhe
AU  - Ma Z
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Shi, Yaxin
AU  - Shi Y
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Zhang, Xirui
AU  - Zhang X
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Yang, Yuan
AU  - Yang Y
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Wang, Jia
AU  - Wang J
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China.
FAU - Fan, Lili
AU  - Fan L
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China. Electronic address: 102337@hrbmu.edu.cn.
FAU - Wu, Lijie
AU  - Wu L
AD  - Department of Children's and Adolescent Health, Public Health College, Harbin 
      Medical University, Harbin, China. Electronic address: wulijiehyd@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230328
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Glutamates)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Autism Spectrum Disorder/genetics
MH  - Quality of Life
MH  - Mice, Inbred Strains
MH  - Pain/genetics
MH  - Glutamates
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Autism spectrum disorder
OT  - Dorsal root ganglia
OT  - Glutamate transporter
OT  - Kir4.1
OT  - Pain sensation abnormality
COIS- Declaration of competing interest The authors declare that they have no competing 
      financial interests or personal relationships that may have influenced the work 
      reported in this study.
EDAT- 2023/03/30 06:00
MHDA- 2023/05/08 10:17
CRDT- 2023/03/29 19:29
PHST- 2022/12/30 00:00 [received]
PHST- 2023/03/19 00:00 [revised]
PHST- 2023/03/21 00:00 [accepted]
PHST- 2023/05/08 10:17 [medline]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/29 19:29 [entrez]
AID - S0925-4439(23)00066-2 [pii]
AID - 10.1016/j.bbadis.2023.166700 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2023 Jun;1869(5):166700. doi: 
      10.1016/j.bbadis.2023.166700. Epub 2023 Mar 28.