Project description:We have recently developed a Drosophila behavioral- and transcriptomic- based (systems) model of chronic pentylenetetrazole (PTZ) induced locomotor plasticity. Pharmacological validation using antiepileptic drugs (AEDs) sodium valproate and levetiracetam (LEV) at behavioral level showed a weaker prophylactic and stronger symptomatic effect of sodium valproate and the opposite, i.e., stronger prophylactic and weaker symptomatic, effect in the model. Microarray gene expression profiling of fly head after sodium valproate and LEV treatment of flies further supported the above therapeutic effect of the two AEDs in the PTZ fly model. Given the strong prophylactic effect of LEV in our model, we hypothesized that time series of transcriptomic alterations caused by PTZ at 12 hrs, 2nd day and 7th day (an earlier GEO submission) may be neutralized by LEV. The present submission relates to microarray expression profiles at 12 hrs, 2nd day and 7th day of a drug regime in which flies were treated with both PTZ and LEV for four days followed by three days of treatment with PTZ alone. Results are consistent with our above hypothesis. Keywords: Drug combination response
Project description:Drosophila melanogaster adult flies fed on food containing 16 mg/ml of pentylenetetrazole (PTZ) in the food show a hyperkinetic behavior within 24 hours. Half of that concentration, i.e., 8 mg/ml, of PTZ, if fed for seven days, though doesn’t cause seizure-like behavior, results in a decreased climbing speed in flies. This change in locomotor behavior is progressive and becomes significant only on seventh day of the treatment. We also examined flies’ locomotor behavior secondary to PTZ withdrawal. Interestingly, an increased climbing speed was found to develop seven days after withdrawal. Importantly, antiepileptic drugs showed effectiveness in the above fly model. Earlier, we submitted in GEO time series of fly head microarray gene expression profiling during chronic PTZ and PTZ withdrawal phase. We also submitted previously expression profiles associated with antiepileptic drug treatment. Here, we have undertaken a different line of work. Having developed a well characterized acquired model of behavioral and gene expression plasticity, we found an opportunity here to investigate if drug exposure to adult males could cause transgenerational effect. To probe this, we carried out a systematic study at both behavioral and microarray gene expression levels. In the latter, we asked the question that do F0 testis, F1 males’ head, F1 females’ head, F1 testis, F2 males’ head and F2 females’ head show gene expression changes if F0 male parents had a history of PTZ exposure? A total of 28 microarray slides were used in this study.