Inhibition of transient potential receptor vanilloid type 1 suppresses seizure susceptibility in the genetically epilepsy-prone rat.
Inhibition of transient potential receptor vanilloid type 1 suppresses seizure susceptibility in the genetically epilepsy-prone rat.
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DOI：
10.1111/cns.12770
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发表时间：
2018-01
影响因子：
5.5
通讯作者：
N'Gouemo P
中科院分区：
文献类型：
--
作者：
Cho SJ;Vaca MA;Miranda CJ;N'Gouemo P
细胞内钙离子在导致癫痫发作的神经元过度兴奋中起重要作用。一种感兴趣的钙内流途径是瞬时受体电位香草酸1型（TRPV 1）通道。在这里，我们评估了辣椒平（CPZ），一种有效的TRPV 1通道阻断剂对遗传性癫痫易感大鼠（GEPR-3），一种遗传性癫痫模型的声诱发癫痫发作（听源性癫痫发作，AGS）的影响。使用雄性和雌性GEPR-3。对于急性CPZ治疗研究，在用各种剂量的CPZ（0、1、3和10 mg/kg; i. p.）治疗之前和之后测试GEPR-3的AGS敏感性。用于半慢性CPZ治疗研究。在以1 mg/kg（i. p.）的剂量进行5天CPZ处理之前和之后，测试GEPR-3的AGS敏感性。记录并分析AGS的患病率、潜伏期和严重程度。我们发现，急性CPZ预处理降低了男性GEPR-3的癫痫发作的严重程度，效果是剂量依赖性的。然而，在女性GEPR-3中，CPZ治疗完全抑制了癫痫发作的易感性。此外，半慢性CPZ治疗抑制了女性GEPR-3的癫痫发作易感性，但仅降低了男性GEPR-3的癫痫发作严重程度。这些发现表明TRPV 1通道是抑制癫痫发作的有希望的分子靶点，女性GEPR-3s表现出比男性GEPR-3s更高的敏感性。
Intracellular calcium plays an important role in neuronal hyperexcitability that leads to seizures. One calcium influx route of interested is the transient receptor potential vanilloid type 1 (TRPV1) channel. Here, we evaluated the effects of capsazepine (CPZ), a potent blocker of TRPV1 channels on acoustically evoked seizures (audiogenic seizures, AGS) in the genetically epilepsy-prone rat (GEPR-3), a model of inherited epilepsy. Male and female GEPR-3s were used. For the acute CPZ treatment study, GEPR-3s were tested for AGS susceptibility before and after treatment with various doses of CPZ (0, 1, 3, and 10 mg/kg; i.p.). For semichronic CPZ treatment study. GEPR-3s were tested for AGS susceptibility before and after 5-day CPZ treatment at the dose of 1 mg/kg (i.p.). The prevalence, latency, and severity of AGS were recorded and analyzed. We found that acute CPZ pre-treatment reduced the seizure severity in male GEPR-3s; the effect was dose-dependent. In female GEPR-3s, however, CPZ treatment completely suppressed the seizure susceptibility. Furthermore, semi-chronic CPZ treatment suppressed seizure susceptibility in female GEPR-3s, but only reduced the seizure severity in male GEPR-3s. These findings suggest that the TRPV1 channel is a promising molecular target for seizure suppression, with female GEPR-3s exhibiting higher sensitivity than male GEPR-3s.
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影响因子：
5.3
作者：
Bhaskaran, Muthu D.;Smith, Bret N.
通讯作者：
Smith, Bret N.
影响因子：
3.3
作者：
Cristino, L.;De Petrocellis, L.;Di Marzo, V.
通讯作者：
Di Marzo, V.
影响因子：
2.2
作者：
Manna, Shyamshree S. S.;Umathe, Sudhir N.
通讯作者：
Umathe, Sudhir N.
影响因子：
6.1
作者：
BROWNING, RA
通讯作者：
BROWNING, RA
TRPV1 功能的干扰改变了 PTZ 诱发癫痫发作的易感性。
影响因子：
5.3
作者：
Jia YF;Li YC;Tang YP;Cao J;Wang LP;Yang YX;Xu L;Mao RR
通讯作者：
Mao RR