Welcome back to the blog!
Week two of working on epilepsy research under the McNamara Lab has flown by! Much of my time has been devoted to working with the ImageJ software used to analyze our research, but I’ve also split my time amongst digesting mice tails, running PCRs and gels to analyze genotypes, and even reorganizing our EEG rig that we use to monitor the electrical activity of our experimental mice. I also got to shadow an RNAscope procedure which will become crucial to my project that studies some of the molecular mechanisms related to epilepsy.
To explain more about the focus of my project, 30% of patients with temporal lobe epilepsy (TLE) don’t respond to the approximately 30 anti-seizure drugs available in the U.S which only help manage symptoms of the condition. Given this gap left by current treatment options, understanding the mechanisms behind TLE development and progression can inform the development of new therapies.
Research conducted by other scientists has shown that an episode of prolonged seizures is enough to promote epileptogenesis. This process has been attributed to the activation of the tyrosine kinase TrkB, a receptor for BDNF. On the other hand, briefly inhibiting TrkB signaling following a seizure unexpectedly caused epileptogenesis to regress suggesting the existence of a seizure-activated “anti-epileptogenic” pathway. Yet, without a recent seizure inhibiting BDNF/TrkB signaling had no effect.
These findings lead us to question what pathways are involved in the inhibition of epileptogenesis, and one receptor tyrosine kinase of interest is Neuregulin 1 activated ErbB4. The effects of activating and inhibiting Nrg1/ErbB4 signaling suggest that seizure-induced activation of this pathway inhibits epileptogenesis. Finally, by applying RNAscope my summer project hopes to highlight the neural circuits and cells in which seizures activate Nrg1/ErbB4 signaling.
Until next week,
Emma Podol
