Drosophila transcriptomic and behavioral model detects potassium chloride with therapeutic potential

In a newly described Drosophila model, two of the five antiepileptic drugs (AEDs) tested, sodium valproate (NaVP) and levetiracetam (LEV), not ethosuximide (ETH), gabapentin (GBP) and vigabatrin (VGB), ameliorate development of chronic pentylenetetrazole (PTZ) induced locomotor alteration. To further characterize the model, we analyze here the microarray expression profile of heads of flies treated with depolarizing compound potassium chloride (KCl). Surprisingly, microarray clustering showed unexpected similarity among KCl, LEV and NaVP. Further, like the two effective AEDs in the fly model, KCl regulated genes overrepresented ribosomal pathway. Interestingly, KCl also ameliorated development of locomotor deficit in the chronic PTZ model. Both transcriptomic and behavioral analyses thus showed LEVand NaVPlike neuroprotective effect of KCl. This is consistent with neuroprotective effect of KCl observed previously in mammalian system. The Drosophila model thus provides a unique opportunity to understand long term mechanisms of neuroactive compounds.