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Augmented impulsive behavior in febrile seizure-induced mice

Abstract

Febrile seizure (FS) is one of the most prevalent etiological events in childhood affecting 2–5% of children from 3 months to 5 years old. Debates on whether neurodevelopmental consequences rise in later life following a febrile seizure or not are still ongoing however there is limited evidence of its effect, especially in a laboratory setting. Moreover, the comparative study using both male and female animal models is sparse. To examine the effect of FS on the behavioral features of mice, both sexes of ICR mice were induced with hyperthermic seizures through exposure to an infrared heat lamp. The mice were divided into two groups, one receiving a single febrile seizure at postnatal day 11 (P11) and one receiving three FS at P11, P13, and P15. Starting at P30 the FS-induced mice were subjected to a series of behavioral tests. Mice with seizures showed no locomotor and motor coordination deficits, repetitive, and depressive-like behavior. However, the FS-induced mice showed impulsive-like behavior in both elevated plus maze and cliff avoidance tests, which is more prominent in male mice. A greater number of mice displayed impaired CAT in both males and females in the three-time FS-induced group compared to the single induction group. These results demonstrate that after induction of FS, male mice have a higher susceptibility to consequences of febrile seizure than female mice and recurrent febrile seizure has a higher chance of subsequent disorders associated with decreased anxiety and increased impulsivity. We confirmed the dysregulated expression of impulsivity-related genes such as 5-HT1A and tryptophan hydroxylase 2 from the prefrontal cortices of FS-induced mice implying that the 5-HT system would be one of the mechanisms underlying the increased impulsivity after FS. Taken together, these findings are useful in unveiling future discoveries about the effect of childhood febrile seizure and the mechanism behind it.

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Acknowledgements

This paper was supported by Konkuk University in 2020.

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This paper was supported by Konkuk University in 2020.

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CGR, ELG, and KJA performed the behavioral experiments. SJJ verified the analytical methods. CYS conceived of the presented idea and also supervised the findings of this work. CGR, SJJ, and CYS wrote the manuscript. All authors discussed the results and contributed to the final manuscript.

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Correspondence to Chan Young Shin.

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Remonde, C.G., Gonzales, E.L., Adil, K.J. et al. Augmented impulsive behavior in febrile seizure-induced mice. Toxicol Res. (2022). https://doi.org/10.1007/s43188-022-00145-1

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Keywords

  • Febrile seizure
  • Animal model
  • Impulsive behavior
  • 5-HT1A
  • Developmental period