Sex and estrous cycle stage shape left-right asymmetry in chronic hippocampal seizures in mice.
Sex and estrous cycle stage shape left-right asymmetry in chronic hippocampal seizures in mice.
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小鼠慢性海马癫痫发作的性别和动情周期阶段形状左右不对称。
DOI：
10.1101/2023.01.20.524965
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Christian-Hinman,CatherineA
中科院分区：
文献类型：
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作者：
Cutia,CathrynA;Leverton,LeannaK;Christian-Hinman,CatherineA
海马功能偏侧是由选择性影响该结构的一个半球的神经系统疾病（如颞叶癫痫（TLE））患者的不同结果所指示的。TLE海马内kainic酸（IHKA）注射模型允许对左侧或右侧海马进行靶向损伤，从而可以系统地比较左右不对称对癫痫发作和非癫痫发作结果的影响。尽管最近在该模型中评估了基于海马背侧注射侧的不同非癫痫表型结果，但左注射（IHKA- l）与右注射（IHKA- r） IHKA动物慢性癫痫发作模式的差异尚未得到评估。在这里，我们评估了雄性和雌性IHKA-L和IHKA-R小鼠的海马癫痫发作发生率。与男性相比，女性在注射后2个月和4个月的电图癫痫活动都有所增加。此外，IHKA-L雌鼠在发情期和发情期的发作频率高于IHKA-R，但发作持续时间和发作时间百分比仅在发情期高于IHKA-L雌鼠。然而，这些周期阶段相关的变化并没有持续到注射后4个月。此外，在男性中没有观察到这种癫痫发作负担的偏侧差异。这些结果首次表明，IHKA注射侧可以形成慢性电图癫痫发作负担。总的来说，这些结果表明，雌性海马功能的左右不对称可以与发情周期阶段相互作用，形成癫痫小鼠的慢性发作，这对正常和疾病状态下的神经活动和行为都有影响。
Lateralization of hippocampal function is indicated by varied outcomes of patients with neurologic disorders that selectively affect one hemisphere of this structure, such as temporal lobe epilepsy (TLE). The intrahippocampal kainic acid (IHKA) injection model of TLE allows for targeted damage to the left or right hippocampus, enabling systematic comparison of effects of left-right asymmetry on seizure and nonseizure outcomes. Although varying nonseizure phenotypic outcomes based on injection side in dorsal hippocampus were recently evaluated in this model, differences in chronic seizure patterns in left- (IHKA-L) versus right-injected (IHKA-R) IHKA animals have yet to be evaluated. Here, we assessed hippocampal seizure incidence in male and female IHKA-L and IHKA-R mice. Females displayed increased electrographic seizure activity compared with males at both two and four months postinjection. In addition, IHKA-L females showed higher seizure frequency than IHKA-R on diestrus and estrus at two months postinjection, but seizure duration and percent time in seizures were only higher in IHKA-L females on diestrus. These cycle stage-associated changes, however, did not persist to four months postinjection. Furthermore, this lateralized difference in seizure burden was not observed in males. These results indicate for the first time that the side of IHKA injection can shape chronic electrographic seizure burden. Overall, these results demonstrate a female-specific left-right asymmetry in hippocampal function can interact with estrous cycle stage to shape chronic seizures in mice with epilepsy, with implications for neural activity and behavior in both normal and disease states.