Saras Arunesh, Tanouye Mark A
Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720
Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720 Department of Molecular and Cell Biology, University of California Berkeley, California 94720.
G3 (Bethesda). 2016 Oct 13;6(10):3381-3387. doi: 10.1534/g3.116.034629.
Bang-sensitive (BS) Drosophila mutants display characteristic seizure-like activity (SLA) and paralysis after mechanical shock . After high-frequency electrical stimulation (HFS) of the brain, they generate robust seizures at very low threshold voltage. Here we report an important phenomenon, which effectively suppresses SLA in BS mutants. High temperature causes seizure suppression in all BS mutants (para, eas, sda) examined in this study. This effect is fully reversible and flies show complete recovery from BS paralysis once the temperature effect is nullified. High temperature induces an increase in seizure threshold after a brief pulse of heat shock (HS). By genetic screening, we identified the involvement of cAMP in the suppression of seizures by high temperature. We propose that HS induces adenylyl cyclase which in turn increases cAMP concentration which eventually suppresses seizures in mutant flies. In summary, we describe an unusual phenomenon, where high temperature can suppress SLA in flies by modulating cAMP concentration.
对重击敏感(BS)的果蝇突变体在受到机械冲击后会表现出典型的癫痫样活动(SLA)和麻痹。对大脑进行高频电刺激(HFS)后,它们在非常低的阈值电压下就会引发强烈的癫痫发作。在此,我们报告一个重要现象,该现象能有效抑制BS突变体中的SLA。高温可使本研究中检测的所有BS突变体(para、eas、sda)的癫痫发作得到抑制。这种效应完全可逆,一旦温度效应消除,果蝇就能从BS麻痹中完全恢复。短暂的热休克(HS)脉冲后,高温会导致癫痫发作阈值升高。通过基因筛选,我们确定了cAMP参与高温对癫痫发作的抑制作用。我们提出,HS诱导腺苷酸环化酶,进而增加cAMP浓度,最终抑制突变果蝇的癫痫发作。总之,我们描述了一种不寻常的现象,即高温可通过调节cAMP浓度来抑制果蝇的SLA。