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Transcriptomic analysis implicates ribosomal and energy metabolic pathways in antiepileptic drug action in a Drosophila model

Priyanka Singh¹, Farhan Mohammad² & Abhay Sharma¹

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1. Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Delhi University campus, Mall Road, Delhi 110007
2. Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Delhi University campus, Mall Road, Delhi 110007.

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Document Type:

Manuscript

Date:

Received 03 July 2009 14:57 UTC; Posted 07 July 2009

Subjects:

Genetics & Genomics, Neuroscience, Pharmacology, Bioinformatics

Tags:

• antiepileptic drugs
• valproate
• gabapentin
• vigabatrin
• ethosuximide
• levetiracetam
• pentylenetetrazole
• Drosophila
• gene expression
• microarray
• transcriptomic

Abstract:

Mechanisms of long term action of antiepileptic drugs (AEDs), used in treating epilepsy and many other neurological and psychiatric disorders, are poorly understood. Recently, a novel Drosophila transcriptomic model of locomotor plasticity induced by chronic pentylenetetrazole (PTZ), a chemoconvulsant commonly used to model epileptogenesis and test AEDs in rodents, has been described. In this model, two of the five AEDs tested, sodium valproate (NaVP) and levetiracetam (LEV), not ethosuximide (ETH), gabapentin (GBP) and vigabatrin (VGB), ameliorate development of chronic PTZ induced locomotor alteration. Here, we describe transcriptomic effect of the AEDs in the fly model. Singular treatment with ETH, GBP and VGB in general caused downregulation of genes. In contrast, similar treatment with NaVP and LEV caused upregulation. The GBP and NaVP gene sets showed enrichment of the ribosomal and energy metabolic pathways. The network partners of ETH, VGB and LEV regulated genes in the available interactome map were also found to overrepresent the ribosomal pathway. Unlike PTZ alone, PTZ and LEV combination treatment was found to cause differential regulation of genes that too enriched the ribosomal and energy metabolic pathways. Cumulatively, we provide transcriptomic evidence that suggests involvement of ribosomal and energy metabolic mechanisms in AED action. The Drosophila model provides an excellent opportunity to further understand mechanisms of AED action 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. Transcriptomic analysis implicates ribosomal and energy metabolic pathways in antiepileptic drug action in a Drosophila model. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3396.1> (2009)

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