Zebrafish offer the potential for a primary screen to identify a wide variety of potential anticonvulsants

被引:180
作者
Berghmans, Stephane
Hunt, Julia
Roach, Alan
Goldsmith, Paul [1 ]
机构
[1] Addenbrookes Hosp, Dept Neurol, Cambridge CB2 0QQ, England
[2] DanioLabs Ltd, Cambridge CB25 9TN, England
关键词
epilepsy; zebrafish; pentylene tetrazole; screen; AEDs;
D O I
10.1016/j.eplepsyres.2007.03.015
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The search for novel anticonvulsants requires appropriate model systems in which to test hypotheses through focused compound screening or genetic manipulation, or conduct black box screening of large numbers of compounds or potential genetic modifiers. Many models are currently in existence that subserve particular roles in achieving these aims, but all have their limitations. Zebrafish have been suggested as an additional model of. epilepsy, but their optimum role is unclear. They are more amenable to high throughput analysis, but are more genetically removed from humans than rodents. We therefore sought to develop assay methodology applicable to medium/high throughput screening using an automated tracking system to measure the amount of movement induced by exposure to the proconvulsant, pentylene tetrazole (PTZ). We then used this system to explore how many known anti-epileptic drugs (AEDs) would be detected when running such a screen. We were able to detect suppression of PTZ-induced excessive movements with 13 out of 14 standard AEDs. A parallel sedation and toxicity screen suggested these effects were due to direct anti-epileptic effect, although non-specific effects cannot be fully excluded. These results suggest zebrafish may be a useful high throughput primary screen to pick up potential novel AEDs. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:18 / 28
页数:11
相关论文
共 24 条
[1]   Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-FoS expression [J].
Baraban, SC ;
Taylor, MR ;
Castro, PA ;
Baier, H .
NEUROSCIENCE, 2005, 131 (03) :759-768
[2]   Making waves in cancer research: new models in the zebrafish [J].
Berghmans, S ;
Jette, C ;
Langenau, D ;
Hsu, K ;
Stewart, R ;
Look, T ;
Kanki, JP .
BIOTECHNIQUES, 2005, 39 (02) :227-237
[3]   Overview of the zebrafish system [J].
Detrich, HW ;
Westerfield, M ;
Zon, LI .
METHODS IN CELL BIOLOGY, VOL 59: ZEBRAFISH: BIOLOGY, 1999, 59 :3-10
[4]  
Driever W, 1996, DEVELOPMENT, V123, P37
[5]   ANIMAL-MODELS OF THE EPILEPSIES [J].
FISHER, RS .
BRAIN RESEARCH REVIEWS, 1989, 14 (03) :245-278
[6]   Zebrafish as a pharmacological tool: the how, why and when [J].
Goldsmith, P .
CURRENT OPINION IN PHARMACOLOGY, 2004, 4 (05) :504-512
[7]   STAGES OF EMBRYONIC-DEVELOPMENT OF THE ZEBRAFISH [J].
KIMMEL, CB ;
BALLARD, WW ;
KIMMEL, SR ;
ULLMANN, B ;
SCHILLING, TF .
DEVELOPMENTAL DYNAMICS, 1995, 203 (03) :253-310
[8]   Zebrafish: a new model on the pharmaceutical catwalk [J].
Langheinrich, U .
BIOESSAYS, 2003, 25 (09) :904-912
[9]  
LOSCHER W, 1984, METHOD FIND EXP CLIN, V6, P531
[10]   LANDMARK ARTICLE - SODIUM DIPHENYL HYDANTOINATE IN THE TREATMENT OF CONVULSIVE DISORDERS (REPRINTED) [J].
MERRITT, HH ;
PUTNAM, TJ .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1984, 251 (08) :1062-1067