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Attenuation of pentylenetrazole-induced acute status epilepticus in rats by adenosine involves inhibition of the mammalian target of rapamycin pathway

Wang, Yulianga,b,*; Liu, Xuewua,*; Wang, Yuanb,*; Chen, Jinbob; Han, Taoa; Su, Leia; Zang, Kejuna

doi: 10.1097/WNR.0000000000000878
CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCE
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Adenosine (ADO) has been characterized as an endogenous anticonvulsant and alternative therapeutic drug, but its mechanism is not entirely clear. This study aimed to examine the relationship of ADO with the mammalian target of rapamycin (mTOR) in a Wistar rat model of pentylenetetrazole (PTZ)-induced acute status epilepticus. ADO (200 mg/kg) was administered intraperitoneally 30 min before PTZ (55–65 mg/kg) treatment, and Western blot assays and immunohistochemistry were performed 3 h after the onset of acute status epilepticus to detect phospho-TOR and the downstream target of mTOR, phospho-S6. The expression of these phosphoproteins in the hippocampus was significantly increased in PTZ-treated rats, but this increase was attenuated by the addition of ADO. To further verify a role for ADO in attenuating mTOR activity, we also evaluated its ability to suppress mTOR activity in normal rats that were not treated with PTZ. Our results suggest that ADO suppresses mTOR and S6 phosphorylation in normal rats and that this suppression can be reversed by the application of Compound C, an inhibitor of AMP-activated protein kinase, which functions as an upstream suppressor of the mTOR pathway. Thus, our results provide a novel antiepileptic mechanism for ADO in suppressing mTOR pathway activation upon PTZ-induced acute status epilepticus.

aDepartment of Neurology, Qilu Hospital of Shandong University, Jinan

bBinzhou Medical University Hospital, Binzhou, Shandong, China

*Yuliang Wang, Xuewu Liu, Yuan Wang contributed equally to the writing of this article.

Correspondence to Xuewu Liu, MD, PhD, Department of Neurology, Qilu Hospital of Shandong University, 107 Jinan Culture road, Jinan 256600, ShanDong, China Tel: +86 531 821 69114; e-mail: snlxw1966@163.com

Received June 22, 2017

Accepted July 18, 2017

© 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins