Data/hora: 03/06/2024 01:25:20

Provedor de dados: | Nature Precedings
País: | United Kingdom
Título: | A novel _Drosophila_ post-genomic CNS drug discovery model detects tetraethylammonium chloride with therapeutic potential
Autores: | Priyanka Singh; Farhan Mohammad*; Abhay Sharma.
Data: | 2009-07-10
Ano: | 2009
Palavras-chave: | Genetics &amp; Genomics; Neuroscience; Pharmacology; Bioinformatics.
Resumo: | A _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.
Tipo: | Manuscript

Identificador:

http://precedings.nature.com/documents/3418/version/1

oai:nature.com:10101/npre.2009.3418.1

http://hdl.handle.net/10101/npre.2009.3418.1

Fonte: | Nature Precedings
Fonte: | Creative Commons Attribution 3.0 License