A novel Drosophila model of pentylenetetrazole withdrawal induced brain plasticity: behavioral and functional genomic characterization

Abstract

Systems biology is an emerging field that promises understanding of the entirety of processes that happen in a biological system, a long awaited objective of the biological sciences. Whereas molecules such as RNA and proteins are the focus of molecular biology, systems biology relates to entire system as a whole with molecules as components. The aim of systems approach is to comprehend the functioning of complex biological systems so that predictive models of human diseases could be developed. Because of enormous complexity of higher organisms, the focus of systems biology is currently on simpler organisms. It is in this backdrop that development of a Drosophila systems model of pentylenetetrazole (PTZ) induced locomotor plasticity responsive to antiepileptic drugs (AEDs) was undertaken. Chronic PTZ treatment is an established means to induce kindling in rodents. A model of brain plasticity, kindling involves recurrent activation of neural pathways that results in an increased susceptibility to evoked seizures and ultimately progresses to spontaneous seizures. Rodent kindling is widely used to model epileptogenesis. Epileptogenesis involves processes whereby structural and functional changes occur in the brain after an insult/ injury resulting in epilepsy. Kindling-like phenomena is also considered relevant in various neuropsychiatric conditions. AEDs are also used in treating, besides epilepsy, various other neurological and psychiatric conditions. Only a limited understanding exists at present as to how the initial electrographic seizure-induced changes in synaptic transmission and gene expression relate to permanent alteration in brain function induced by kindling. A systems level understanding of epileptogenesis is expected to facilitate development of novel antiepileptogenic, disease-modifying, and neuroprotective agents.