Remonde Chilly Gay, Gonzales Edson Luck, Adil Keremkleroo Jym, Jeon Se Jin, Shin Chan Young
School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul, 05029 Republic of Korea.
Toxicol Res. 2022 Jul 29;39(1):37-51. doi: 10.1007/s43188-022-00145-1. eCollection 2023 Jan.
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.
热性惊厥（FS）是儿童期最常见的病因之一，影响2%至5%的3个月至5岁儿童。关于热性惊厥后后期神经发育后果是否增加的争论仍在继续，但其影响的证据有限，尤其是在实验室环境中。此外，使用雄性和雌性动物模型的比较研究很少。为了研究热性惊厥对小鼠行为特征的影响，通过暴露于红外热灯对两性ICR小鼠进行高热惊厥诱导。将小鼠分为两组，一组在出生后第11天（P11）接受单次热性惊厥，另一组在P11、P13和P15接受三次热性惊厥。从P30开始，对热性惊厥诱导的小鼠进行一系列行为测试。惊厥小鼠未表现出运动和运动协调缺陷、重复性和抑郁样行为。然而，热性惊厥诱导的小鼠在高架十字迷宫和悬崖回避试验中均表现出冲动样行为，在雄性小鼠中更为突出。与单次诱导组相比，在三次热性惊厥诱导组中，更多的雄性和雌性小鼠表现出CAT受损。这些结果表明，热性惊厥诱导后，雄性小鼠比雌性小鼠对热性惊厥后果的易感性更高，复发性热性惊厥更有可能导致随后与焦虑降低和冲动增加相关的疾病。我们证实了热性惊厥诱导小鼠前额叶皮质中5-HT1A和色氨酸羟化酶2等冲动相关基因的表达失调，这意味着5-羟色胺系统可能是热性惊厥后冲动增加的潜在机制之一。综上所述，这些发现有助于揭示关于儿童热性惊厥的影响及其背后机制的未来发现。
