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| Priyanka Singh; Farhan Mohammad; Abhay Sharma. |
| Rodent kindling induced by pentylenetetrazole (PTZ) is an established model of epileptogenesis and antiepileptic drug (AED) testing. Recently, a Drosophila systems model has been described in which chronic PTZ causes a decreased climbing speed in adult males on 7th day. Some AEDs ameliorate development of this locomotor deficit. Time-series of microarray expression profiles of heads of flies treated with PTZ has been found to resemble transcriptomic alterations associated with epileptogenesis. In the fly model, withdrawal from seven day long PTZ treatment causes an increased climbing speed on 7th consequent day. Here, we present a systems model of the post-PTZ withdrawal regime. Unlike AED-untreated individuals, flies treated with any of the five AEDs... |
| Tipo: Manuscript |
Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/3447/version/1 |
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| Priyanka Singh; Farhan Mohammad*; Abhay Sharma. |
| 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... |
| Tipo: Manuscript |
Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/3418/version/1 |
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| Farhan Mohammad; Priyanka Singh; Abhay Sharma. |
| 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... |
| Tipo: Manuscript |
Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/3429/version/1 |
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| Abhay Sharma. |
| Pentylenetetrazole (PTZ) has recently been found to ameliorate cognitive impairment in rodent models of Down syndrome (DS). The mechanism underlying PTZ’s therapeutic effect is however not clear. Microarray profiling has previously reported differential expression of genes in DS. No mammalian transcriptomic data on PTZ treatment however exists. Nevertheless, a _Drosophila_ model inspired by rodent models of PTZ induced kindling plasticity has recently been described. Microarray profiling has shown PTZ’s downregulatory effect on gene expression in fly heads. In a comparative transcriptomics approach, I have analyzed the available microarray data in order to identify potential mechanism of PTZ action in DS. I find that transcriptomic... |
| Tipo: Manuscript |
Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics. |
| Ano: 2010 |
URL: http://precedings.nature.com/documents/4330/version/1 |
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| Abhay Sharma; Farhan Mohammad; Priyanka Singh. |
| A male Drosophila model of locomotor deficit induced by chronic pentylenetetrazole (PTZ), a proconvulsant used to model epileptogenesis in rodents, has recently been described. Antiepileptic drugs (AEDs) ameliorate development of this behavioral abnormality. Time-series of microarray profiling of heads of male flies treated with PTZ has shown epileptogenesis-like transcriptomic perturbation in the fly model. Gender differences are known to exist in neurological and psychiatric conditions including epileptogenesis. We describe here the effects of chronic PTZ in Drosophila females, and compare the results with the male model. As in males, chronic PTZ was found found to cause a decreased climbing speed in females. In males, overrepresentation of Wnt, MAPK,... |
| Tipo: Manuscript |
Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/3460/version/1 |
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| Abhay Sharma. |
| Transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics has recently been discovered using a Drosophila systems model. In this novel mode of inheritance, transcriptomic alteration induced by the neuroactive drug pentylenetetrazole (PTZ) has been found to leak to future generations. Here, the available microarray gene expression data pertaining to CNS and/or testis of exposed F0 and the resulting F1 and F2 generations has been pooled and analyzed in an unbiased manner at four levels, namely, biological processes and pathways, protein interactome networks, miRNA-targets, and microarray expression profile similarities. Enrichment for processes related to translation, energy metabolism, cell proliferation, cell... |
| Tipo: Manuscript |
Palavras-chave: Genetics & Genomics. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/3312/version/1 |
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| Priyanka Singh; Farhan Mohammad; Abhay Sharma. |
| 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.... |
| Tipo: Manuscript |
Palavras-chave: Genetics & Genomics; Neuroscience; Pharmacology; Bioinformatics. |
| Ano: 2009 |
URL: http://precedings.nature.com/documents/3396/version/1 |
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