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Neurochemical Research

, Volume 44, Issue 12, pp 2796–2808 | Cite as

Increased Expression of Kv10.2 in the Hippocampus Attenuates Valproic Acid-Induced Autism-Like Behaviors in Rats

  • Jing Wang
  • Shini Feng
  • Min Li
  • Yamei Liu
  • Jinyu Yan
  • Yunfei Tang
  • Dongshu DuEmail author
  • Fuxue ChenEmail author
Original Paper

Abstract

The role of potassium channels provides suggestive evidence for the etiology of autism. The voltage-gated potassium channel Kv10.2 (KCNH5) is widely expressed in the brain. However, the inherent relationship between Kv10.2 and autism is still unclear. Herein, a rat valproic acid (VPA)-induced autism spectrum disorder model was established. The expression level of Kv10.2 was obviously decreased in the hippocampus of VPA rats. Kv10.2 was mainly localized in neurons. Subsequently, a recombinant lentivirus expressing Kv10.2 was used to upregulate the expression of Kv10.2 in the hippocampus of VPA-exposed rats. The results were promising as injection of the Kv10.2 lentivirus in the hippocampus relieved anxiety and stereotypical behavior, and improved the social and exploratory abilities of rats that were prenatally exposed to VPA. In addition, spectral analysis of electroencephalogram data revealed that animals exposed to VPA exhibited increased high-frequency activity compared with the control rats, and this activity recovered to a certain extent after upregulation of Kv10.2 expression by lentivirus injection. These results suggest that changes in Kv10.2 may play an important role in the etiology of autism, thus providing a promising direction for further research on autism.

Keywords

Kv10.2 Valproic acid-induced autism model Electroencephalogram Hippocampus Neuron 

Notes

Acknowledgements

This work was supported by the Shanghai Municipal Science and Technology Commission (Grant No. 16010500600).

Author contributions

JW and SF contributed equally to this work. DD and FC conceived and designed the study. JW, YL and ML performed the experiments at Shanghai University. The first draft of the manuscript was written by JW, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. All persons designated as authors qualify for authorship, and all of those who qualify for authorship are listed.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflict of interest.

Ethical Approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

11064_2019_2903_MOESM1_ESM.tif (19.8 mb)
Fig. s1Neurological and motor hypoplasia in VPA rats (a) Body weight, (b) Eye opening category score, (c) Plane correction, (d) Cliff avoidance, (e) Negative geotaxis, (f) Swimming condition. Data are represented as the mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001 vs. the control group. n = 20. Supplementary material 1 (TIF 21450.9 kb)
11064_2019_2903_MOESM2_ESM.tif (20.9 mb)
Fig. s2Fig. s2 VPA-induced rats exhibited autistic-like behavior. In the three-chamber social interaction assay, social interaction (a) and social novelty preference (b) were recorded. (c) The percentage of time that rats remained in the open arm in the elevated plus maze test was significantly decreased in the VPA group. (d) The percentage of time in the white box was decreased in the VPA group. (e) The time in the central zone in the open field was decreased in VPA-induced rats compared with control rats. (f) VPA-treated rats exhibited more stereotypical behaviors than control rats in the Y maze test. Data are represented as the mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001 vs. the control group. n = 12. Supplementary material 2 (TIF 20313.7 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Life SciencesShanghai UniversityShanghaiChina
  2. 2.Shandong Provincial Key Laboratory of BiopharmaceuticalsShandong Academy of Pharmaceutical SciencesJinanChina

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