Involvement of Scn1b and Kcna1 ion channels in audiogenic seizures and PTZ-induced epilepsy.
We have undertaken chemical genetic approach using Qingyangshenylycosides (QYS), a natural product compound, to explore the molecular mechanisms underlying different types of epilepsy models. Two animal models were used for these studies, i.e., audiogenic seizure (AGS) and pentylenetetrazol (PTZ)-induced generalized epilepsy in DBA/2J mice. We show that the latency of AGS is prolonged and the severity of seizures (the percentages of the tonus, Tonus_%) is reduced in the QYS-treated animals. These results indicate that QYS has anticonvulsant effect on the AGS model. However, we find that administration of QYS has an opposite effects on PTZ-induced generalized epilepsy. Both the latency of the generalized epilepsy and the latency of death are decreased after QYS treatment in PTZ-induced epilepsy. We examine the molecular basis of the distinct roles of QYS in these two epilepsy models by using gene expression data. Our results show that a voltage-gated sodium channel (Scn1b) and a voltage-gated potassium channel (Kcna1) are differentially expressed in AGS and PTZ-induced epilepsy models as well as in QYS-treated animals. Our results demonstrate that a chemical genetic approach may help to reveal both the molecular mechanisms of different epilepsies and the mechanism of action of the antiepileptic drugs.
Li
Xianchun
X
Key Lab of Brain Functional Genomics, MOE&STCSM, Shanghai Institute of Brain Functional Genomics, East China Normal University, 3663 Zhongshan Road, N. Shanghai 200062, China.
Yang
Qingxiong
Q
Kuang
Hui
H
Jiang
Nan
N
Hu
Yinghe
Y
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D020195:Epilepsy, Reflex / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051662:Kv1.1 Potassium Channel / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D010433:Pentylenetetrazole; D012333:RNA, Messenger / Q000096:biosynthesis; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015222:Sodium Channels / Q000378:metabolism*
D000927:Anticonvulsants; D004365:Drugs, Chinese Herbal; C496947:Kcna1 protein, mouse; D012333:RNA, Messenger; D015222:Sodium Channels; D051662:Kv1.1 Potassium Channel; D010433:Pentylenetetrazole