Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Epilepsy Res. 2022 Aug;184:106948. doi: 10.1016/j.eplepsyres.2022.106948. Epub 2022 May 20.
Reproductive endocrine disorders are common comorbidities of temporal lobe epilepsy (TLE). Our previous studies using the intrahippocampal kainic acid (IHKA) mouse model of TLE demonstrated that many females show prolonged estrous cycles and hypothalamic gonadotropin-releasing hormone (GnRH) neurons exhibit elevated firing during diestrus. However, it is unknown whether the degree of change in GnRH neuron activity is dependent on epilepsy severity. Here, we used 24/7 in vivo electroencephalography (EEG) and in vitro electrophysiological recordings in acute brain slices to assess GnRH neuron firing in relation to chronic seizure burden in diestrous female mice at two months after IHKA injection. We found that percentage of time in seizure activity in the 24 h prior to slice preparation is an accurate proxy of overall seizure burden. Firing rates of GnRH neurons from EEG-recorded IHKA mice were increased in comparison to controls, but no relationships were found between GnRH neuron firing and seizure burden measured in vivo. The independence of GnRH neuron firing rate in relation to seizure burden was unaffected by GnRH neuron soma location or estrous cycle length. Furthermore, GnRH neuron firing rates were not yet different from control values when measured 1 month after injection, when epileptogenesis is already complete in IHKA mice. These findings indicate that the severity of epilepsy and the degree of downstream disruption to GnRH neuron activity are independent, suggesting that susceptibility to reproductive endocrine comorbidities is driven by other risk factors.
生殖内分泌紊乱是颞叶癫痫（TLE）的常见合并症。我们之前使用海马内海人酸（IHKA）TLE 小鼠模型的研究表明，许多女性在发情间期表现出延长的发情周期，并且在下丘脑促性腺激素释放激素（GnRH）神经元在发情间期表现出升高的放电。然而，GnRH 神经元活动变化的程度是否取决于癫痫的严重程度尚不清楚。在这里，我们使用 24/7 活体脑电图（EEG）和急性脑切片中的体外电生理记录，评估 IHKA 注射后两个月发情间期雌性小鼠慢性癫痫负荷与 GnRH 神经元放电之间的关系。我们发现，在切片准备前 24 小时内癫痫活动的时间百分比是整体癫痫负荷的准确指标。与对照相比，来自 EEG 记录的 IHKA 小鼠的 GnRH 神经元的放电率增加，但未发现 GnRH 神经元放电与体内测量的癫痫负荷之间存在关系。在 GnRH 神经元体细胞位置或发情周期长度方面，与癫痫负荷相关的 GnRH 神经元放电率的独立性不受影响。此外，当在注射后 1 个月测量时，GnRH 神经元的放电率尚未与对照值有差异，此时 IHKA 小鼠中的癫痫发生已经完成。这些发现表明，癫痫的严重程度和 GnRH 神经元活动下游破坏的程度是独立的，这表明生殖内分泌合并症的易感性是由其他危险因素驱动的。
