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A novel Drosophila post-genomic CNS drug discovery model detects tetraethylammonium chloride with therapeutic potential

Priyanka Singh¹, Farhan Mohammad*² & Abhay Sharma¹

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1. Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Mall Road, Delhi University Campus, Delhi 110007, India
2. Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Mall Road, Delhi University Campus, Delhi 110007, India. *Present address: Tata Institute of Fundamental Research, Department of Biological Research, Dr. Homi Bh

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Document Type:

Manuscript

Date:

Received 10 July 2009 11:55 UTC; Posted 10 July 2009

Subjects:

Genetics & Genomics, Neuroscience, Pharmacology, Bioinformatics

Tags:

• Tetraethylammonium
• pilocarpine
• Drosophila
• neuroprotective
• transcriptomics
• behavior

Abstract:

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.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Singh, Priyanka, Mohammad*, Farhan, and Sharma, Abhay. A novel Drosophila post-genomic CNS drug discovery model detects tetraethylammonium chloride with therapeutic potential. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3418.1> (2009)

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