Metabolic disruption in Drosophila bang-sensitive seizure mutants.
Metabolic disruption in Drosophila bang-sensitive seizure mutants.
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DOI：
10.1534/genetics.106.057463
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发表时间：
2006-07-01
期刊：
影响因子：
3.3
通讯作者：
Ganetzky, Barry
中科院分区：
文献类型：
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作者：
Fergestad, Tim;Bostwick, Bret;Ganetzky, Barry
我们研究了一些果蝇突变体，这些突变体在机械或电刺激后对癫痫发作的敏感性增加，以更好地了解使神经元易于异常活动的潜在因素。这一类中的几个突变已经被分子鉴定，并表明代谢紊乱可能是癫痫易感性增加的一个来源。我们将Bang敏感的癫痫突变敲除(KdN)定位到细胞学位置5F3，并确定柠檬酸合成酶是受影响的基因。这些结果进一步支持线粒体代谢在控制神经元活动和癫痫敏感性中的作用。对bang敏感突变体的生化分析显示，这些突变体中ATP水平的降低与线粒体能量产生的中断一致。对影响线粒体蛋白的突变体进行的电生理学分析显示，癫痫发作活动的特定模式的可能性增加。我们的数据表明细胞代谢在调节癫痫易感性中起作用，并表明神经元亚型对代谢变化的不同敏感性是癫痫活动不同类型的基础。
We examined a number of Drosophila mutants with increased susceptibility to seizures following mechanical or electrical stimulation to better understand the underlying factors that predispose neurons to aberrant activity. Several mutations in this class have been molecularly identified and suggest metabolic disruption as a possible source for increased seizure susceptibility. We mapped the bang-sensitive seizure mutation knockdown (kdn) to cytological position 5F3 and identified citrate synthase as the affected gene. These results further support a role for mitochondrial metabolism in controlling neuronal activity and seizure susceptibility. Biochemical analysis in bang-sensitive mutants revealed reductions in ATP levels consistent with disruption of mitochondrial energy production in these mutants. Electrophysiological analysis of mutants affecting mitochondrial proteins revealed an increased likelihood for a specific pattern of seizure activity. Our data implicate cellular metabolism in regulating seizure susceptibility and suggest that differential sensitivity of neuronal subtypes to metabolic changes underlies distinct types of seizure activity.