Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures.
Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures.
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TRPV1 功能的干扰改变了 PTZ 诱发癫痫发作的易感性。
DOI：
10.3389/fncel.2015.00020
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发表时间：
2015
影响因子：
5.3
通讯作者：
Mao RR
中科院分区：
文献类型：
--
作者：
Jia YF;Li YC;Tang YP;Cao J;Wang LP;Yang YX;Xu L;Mao RR
瞬时受体电位香草素1(TRPV1)广泛分布于包括海马区在内的中枢神经系统(CNS)，调节中枢兴奋与抑制的平衡，在癫痫发病中起重要作用。我们使用药物操作和转基因小鼠来干扰TRPV1的功能，然后研究这些改变对戊四氮(PTZ)诱导的癫痫易感性的影响。结果表明，全身注射TRPV1激动剂辣椒素(CAP，40 mg/kg)可直接诱发强直阵挛发作(TCS)，而不诱发PTZ。CAP低剂量组(5 mg/kg和10 mg/kg)癫痫发作严重程度增加，但TCS潜伏期延迟。另一方面，全身注射TRPV1拮抗剂卡萨西平(CPZ，0.05和0.5 mg/kg)和TRPV1基因敲除小鼠对TCS的潜伏期延长，死亡率降低。此外，首次报道了海马区注射CPZ(10和33nmol/μL/侧)可延长TCS潜伏期，降低癫痫最大发作程度和死亡率。值得注意的是，在海马区TRPV1过度表达的小鼠和给予CAP(33nmol/μL/侧)的小鼠中，观察到PTZ诱发癫痫的敏感性降低，这与全身激动剂CAP的结果相反。我们的研究结果表明，全身应用TRPV1拮抗剂可能是治疗癫痫的新靶点，而海马区TRPV1功能的改变在癫痫易感性中起着关键作用。
Transient receptor potential vanilloid 1 (TRPV1) is widely distributed in the central nervous system (CNS) including hippocampus, and regulates the balance of excitation and inhibition in CNS, which imply its important role in epilepsy. We used both pharmacological manipulations and transgenic mice to disturb the function of TRPV1 and then studied the effects of these alterations on the susceptibility of pentylenetetrazol (PTZ)-induced seizures. Our results showed that systemic administration of TRPV1 agonist capsaicin (CAP, 40 mg/kg) directly induced tonic-clonic seizures (TCS) without PTZ induction. The severity of seizure was increased in lower doses of CAP groups (5 and 10 mg/kg), although the latency to TCS was delayed. On the other hand, systemic administration of TRPV1 antagonist capsazepine (CPZ, 0.05 and 0.5 mg/kg) and TRPV1 knockout mice exhibited delayed latency to TCS and reduced mortality. Furthermore, hippocampal administration of CPZ (10 and 33 nmol/μL/side) was firstly reported to increase the latency to TCS, decrease the maximal grade of seizure and mortality. It is worth noting that decreased susceptibility of PTZ-induced seizures was observed in hippocampal TRPV1 overexpression mice and hippocampal CAP administration (33 nmol/μL/side), which is opposite from results of systemic agonist CAP. Our findings suggest that the systemic administration of TRPV1 antagonist may be a novel therapeutic target for epilepsy, and alteration of hippocampal TRPV1 function exerts a critical role in seizure susceptibility.
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影响因子：
7.3
作者：
MAGGI, CA;BEVAN, S;GIULIANI, S
通讯作者：
GIULIANI, S
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