Gene Expression Profiling of a Hypoxic Seizure Model of Epilepsy Suggests a Role for mTOR and Wnt Signaling in Epileptogenesis

• DOI: 10.1371/journal.pone.0074428
• Publication Date: 2013-09-27T21:18:53Z
• Authors: Joachim Theilhaber; Sanjay N. Rakhade; Judy Sudhalter; Nayantara Kothari; Peter Klein; Jack Pollard; Frances E. Jensen
• Keywords: WNT5A

Microarray profiling was used to investigate gene expression in the hypoxic seizure model of acquired epilepsy rat, with aim characterizing functional pathways which are persistently activated or repressed during epileptogenesis. Hippocampal and cortical tissues were transcriptionally profiled over a one week period following an initial series seizures induced by mild hypoxia at post-natal day 10 (P10), data then analyzed focus on set enrichment analysis, approach emphasizes regulation entire rather than individual genes. Animals subjected three conditions: control no hypoxia, seizures, followed treatment AMPAR antagonist NBQX, compound currently proposed be modulator While temporal samples found consistent known processes neuronal maturation rat for given time window, response enriched components PI3K/mTOR Wnt signaling pathways, alongside sets representative glutamatergic, synaptic axonal processes, perhaps regulated as downstream consequence activation these pathways. also more specifically epileptogenic NBQX-responsive set. mTOR pathway is its role epileptogenesis strengthens case PI3K inhibitors potential anti-epileptogenic drugs, investigation effect appropriate might offer parallel avenue research toward epilepsy.