Abstract
AbstractA Drosophila behavioral and transcriptomic model of locomotor plasticity induced by chronic pentylenetetrazole (PTZ) has recently been developed. In this 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 PTZ induced locomotor alteration. Transcriptomic effect of the AEDs and PTZ in fly head has been described. Here, we analyze microarray expression profile of heads of flies treated with the convulsants tetraethylammonium chloride (TEA) and pilocarpine hydrochloride (PILO). Strikingly, microarray clustering placed TEA, not PILO, with LEV and NaVP in one group that was distinct from the other one consisting of PTZ, GBP, VGB and ETH. Further, like LEV and NaVP, TEA regulated genes overrepresented ribosomal and energy metabolic pathways. Also, TEA, like LEV and NaVP, ameliorated development of locomotor deficit in the chronic PTZ model. Both transcriptomic and behavioral analyses thus demonstrated LEV- and NaVP- like neuroprotective effect of TEA. Our results are consistent with earlier paradoxical evidence suggesting that TEA may be neuroprotective. Amenability of Drosophila model thus provides an excellent opportunity to understand long term mechanisms of action of centrally acting drugs in molecular details.
Highlights
The chemoconvulsant PTZ is used to model epileptogenesis and test antiepileptic drugs (AEDs) in rodents (de Oliveira et al, 2008)
A set of (i) control flies were treated with normal food (NF) in all three vials, (ii) PTZ flies were treated with PTZ in first vial and with NF in second and third vials, (iii) tetraethylammonium chloride (TEA) flies were treated with TEA in first and second vials and with NF in two subsequent vials, and (iv) PTZ+TEA flies were treated with both PTZ and TEA together in first vial, with TEA alone in second vial, and with NF in third vial
TEA behaves like LEV and NaVP in the transcriptomic module
Summary
The chemoconvulsant PTZ is used to model epileptogenesis and test AEDs in rodents (de Oliveira et al, 2008). A novel Drosophila systems model of PTZ induced locomotor plasticity responsive to antiepileptic drugs has been developed (Mohammad et al, 2009). In this model, seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decreased and an increased climbing speed in Drosophila adults. Microarray expression profiling of heads of flies treated with PTZ has shown that the drug induces down-, not up-, regulation of genes (Mohammad et al, 2009). The Drosophila gene expression model has been found to be consistent with transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic patients (Mohammad et al, 2009)
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