Journal
NEUROPHARMACOLOGY
Volume 162, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2019.107760
Keywords
alpha-asaronol; Seizures; PPAR gamma; GW9662; Zebrafish
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Funding
- National Natural Science Foundation of China [81802629]
- Youth Fund of Shandong Academy of Sciences [2018QN0024]
- Chinese Academy of Sciences (Shenyang branch) Shandong Academy of Sciences Partner Program for young scientists
- Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China [IRT_15R55]
- Project of Scientific Research Program of Shanxi Education Department [09JS086]
- European Union's Horizon 2020 research and Innovation programme [734862]
- Marie Curie Actions (MSCA) [734862] Funding Source: Marie Curie Actions (MSCA)
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In mammals, peroxisome proliferators activated receptors (PPARs), the nuclear hormone receptors, have been reported to be involved in seizure control. Selective agonists and antagonists of PPARs raise seizure thresholds and suppress seizures, respectively. In this study, we evaluated the anticonvulsant effects of alpha-asaronol, a metabolic product of a-asarone, on pentylenetetrazole (PTZ)-induced seizures in zebrafish and investigated the underlying mechanisms. As a result, alpha-asaronol ameliorated seizures with increase of seizure latency, as well as decrease of seizure-like behavior, c-fos expression, and abnormal neuronal discharge in a concentration dependent manner. By comparing gene expression profiles of zebrafish undergoing seizures and alpha-asaronol pretreated zebrafish, we found that alpha-asaronol attenuate seizures through increase of PPAR gamma expression, while PPAR gamma antagonist GW9662 inhibit the anti-seizures actions of alpha-asaronol. Moreover, molecular docking simulation implied the physical interaction between alpha-asaronol and PPAR gamma. The overall results indicated that the anticonvulsant effects of alpha-asaronol are regulated through PPAR gamma-mediated pathway, which shed light on development of alpha-asaronol as a potential antiepileptic drug. In addition, it is for first time to report that PPAR gamma is associated with seizures in zebrafish, supporting previous evidence that zebrafish is a suitable alternative for studying seizures.
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