Modulating Behavior in C. elegans Using Electroshock and Antiepileptic Drugs.
Modulating Behavior in C. elegans Using Electroshock and Antiepileptic Drugs.
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DOI：
10.1371/journal.pone.0163786
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Dawson-Scully K
中科院分区：
文献类型：
--
作者：
Risley MG;Kelly SP;Jia K;Grill B;Dawson-Scully K
显微线虫秀丽隐杆线虫已成为一个有价值的模型，了解神经系统疾病的分子和细胞基础。蠕虫提供了重要的生理相似性哺乳动物模型，如保守的神经元形态，离子通道和神经递质。虽然在C. elegans，电休克/电惊厥的测定仍然缺乏。在这里，我们开发了一种定量的行为学方法来评估电击后C。优雅电击会损害正常的运动，并诱发瘫痪和肌肉抽搐;经过短暂的恢复期，受电击的动物恢复正常的运动。我们测试了unc-25（编码GABA生物合成酶GAD）和unc-49（编码GABAA受体）功能丧失突变体的电击反应。与野生型相比，unc-25和unc-49突变体减少了对肌肉的抑制性GABA能传递，并且在电击后需要显著更多的时间来恢复正常运动。重要的是，unc-25和unc-49突变体对电击的敏感性增加可以通过抗癫痫药物（如瑞替加滨）治疗来挽救。此外，我们还发现戊四氮（PTZ）是一种GABAA受体拮抗剂，在哺乳动物和C。elegans癫痫发作模型，增加蠕虫对电击的敏感性。
The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C. elegans. Electric shock impairs normal locomotion, and induces paralysis and muscle twitching; after a brief recovery period, shocked animals resume normal locomotion. We tested electric shock responses in loss-of-function mutants for unc-25, which encodes the GABA biosynthetic enzyme GAD, and unc-49, which encodes the GABAA receptor. unc-25 and unc-49 mutants have decreased inhibitory GABAergic transmission to muscles, and take significantly more time to recover normal locomotion following electric shock compared to wild-type. Importantly, increased sensitivity of unc-25 and unc-49 mutants to electric shock is rescued by treatment with antiepileptic drugs, such as retigabine. Additionally, we show that pentylenetetrazol (PTZ), a GABAA receptor antagonist and proconvulsant in mammalian and C. elegans seizure models, increases susceptibility of worms to electric shock.
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影响因子：
3.7
作者：
Faumont S;Rondeau G;Thiele TR;Lawton KJ;McCormick KE;Sottile M;Griesbeck O;Heckscher ES;Roberts WM;Doe CQ;Lockery SR
通讯作者：
Lockery SR
影响因子：
2.5
作者：
Kautu BB;Carrasquilla A;Hicks ML;Caldwell KA;Caldwell GA
通讯作者：
Caldwell GA
影响因子：
6.7
作者：
Breger J;Fuchs BB;Aperis G;Moy TI;Ausubel FM;Mylonakis E
通讯作者：
Mylonakis E
DOI：
10.1016/j.cub.2015.09.040
发表时间：
2015-11-16
期刊：
Current biology : CB
影响因子：
--
作者：
Giachello CN;Baines RA
通讯作者：
Baines RA
DOI：
10.14581/jer.15010
发表时间：
2015-12-01
期刊：
Journal of epilepsy research
影响因子：
--
作者：
Friedman, L K;Slomko, A M;Ali, S S
通讯作者：
Ali, S S