Epilepsy-associated increase in gonadotropin-releasing hormone neuron firing in diestrous female mice is independent of chronic seizure burden severity.
Epilepsy-associated increase in gonadotropin-releasing hormone neuron firing in diestrous female mice is independent of chronic seizure burden severity.
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DOI：
10.1016/j.eplepsyres.2022.106948
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发表时间：
2022-08
影响因子：
2.2
通讯作者：
Christian-Hinman, Catherine A.
中科院分区：
文献类型：
--
作者：
Li, Jiang;Christian-Hinman, Catherine A.
生殖内分泌紊乱是颞叶癫痫（TLE）的常见合并症。我们以前的研究使用海马内红藻氨酸（IHKA）小鼠模型的TLE表明，许多女性表现出延长的发情周期和下丘脑促性腺激素释放激素（GnRH）神经元表现出升高的放电在间情期。然而，目前尚不清楚GnRH神经元活性的变化程度是否取决于癫痫的严重程度。在这里，我们使用24/7在体内脑电图（EEG）和体外电生理记录在急性脑切片评估GnRH神经元放电与慢性癫痫发作负荷在diestrous雌性小鼠在两个月后注射IHKA。我们发现，在切片制备前24小时内癫痫发作活动的时间百分比是整体癫痫发作负担的准确代表。与对照组相比，EEG记录的IHKA小鼠GnRH神经元的放电率增加，但在体内测量的GnRH神经元放电和癫痫发作负荷之间没有发现关系。GnRH神经元放电频率与癫痫发作负荷的独立性不受GnRH神经元索马位置或发情周期长度的影响。此外，注射后1个月测量时，GnRH神经元放电率与对照值没有差异，此时IKKA小鼠的癫痫发生已经完成。这些发现表明癫痫的严重程度和下游GnRH神经元活动的破坏程度是独立的，表明生殖内分泌共病的易感性是由其他风险因素驱动的。
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 hours 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.
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