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Akt Inhibitor Perifosine Prevents Epileptogenesis in a Rat Model of Temporal Lobe Epilepsy

Neuroscience Bulletin 2018年第2期34卷 283-290页

作者： Feng Zhu Jiejing Kai Linglin Chen Meiling Wu Jingyin Dong Qingmei Wang Ling-Hui Zeng Department of Clinical Medicine School of MedicineZhejiang University City College Department of Pharmacology Zhejiang University School of Medicine

Accumulating data have revealed that abnormal activity of the mTOR(mammalian target of rapamycin)pathway plays an important role in epileptogenesis triggered by various factors. We previously reported that pretreatment with perifosine, an inhibitor of Akt(also called protein kinase B), abolishes the rapamycin-induced paradoxical increase of S6 phosphorylation in a rat model induced by kainic acid(KA). Since Akt is an upstream target in the mTOR signaling pathway, we set out to determine whether perifosine has a preventive effect on epileptogenesis. Here, we explored the effect of perifosine on the model of temporal epilepsy induced by KA in rats and found that pretreatment with perifosine had no effect on the severity or duration of the KA-induced status epilepticus. However, perifosine almost completely inhibited the activation of p-Akt and p-S6 both acutely and chronically following the KA-induced status *** pretreatment suppressed the KA-induced neuronal death and mossy fiber sprouting. The frequency of spontaneous seizures was markedly decreased in rats pretreated with perifosine. Accordingly, rats pretreated with perifosine showed mild impairment in cognitive functions. Collectively, this study provides novel evidence in a KA seizure model that perifosine may be a potential drug for use in anti-epileptogenic therapy.

关键词： Akt-mTOR signaling Perifosine Kainic acid spontaneous seizure Cognitive function

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seizure threshold alteration during the latent period following pilocarpine-induced SE in rats

Seizure threshold alteration during the latent period follow...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Zheng-Hao XU,Yi WANG,Chen-Lin XU,Miao-Miao JIN,Zhong CHEN~* Department of Pharmacology Key Laboratory of Medical Neurobiology of Ministry of Health of China Zhejiang Province Key Laboratory of Neurobiology School of Basic Medical Sciences College of Pharmaceutical Sciences, Zhejiang University,Hangzhou 310058,China

＜正＞Epilepsy is the third most common chronic brain disorder,however,little is known about the underlying *** present study is aimed to investigate whether epileptogenesis for spontaneous seizure is represent a decrease in seizure threshold and how the seizure threshold is altered during the latent period following pilocarpine induced *** stimulation（60 Hz,1 ms,60-300 A） was used every other day for testing the seizure threshold. The duration of the latent period was determined by continuous video/EEG *** results showed that electrical threshold significantly increased after SE and decreased to pre-SE state in 10-25 d after SE in SE group, in which spontaneous seizures were observed in all animals within 30 ***,in Non-SE group,threshold significantly decreased after pilocarpine treatment and maintained in the following *** spontaneous seizures were found in these animals in the following 50 d after pilocarpine *** sham group where animals were treated with saline,threshold was slightly decreased because of electrical stimulation every other *** study indicates that epileptogenesis in the latent period is not just a seizure threshold-deceasing period,and seizure threshold increasing but not deceasing in the latent period may be the key for the subsequent spontaneous seizure.

关键词： seizure threshold pilocarpine epileptogenesis spontaneous seizure

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