Brain Institute Investigator John White, Ph.D., and Professor of Pharmacology and Toxicology Karen Wilcox, Ph.D., were awarded $1.7 Million from the National Institute of Neurological Disorders and Stroke, and $300,000 from the Ben B. and Iris M. Margolis Foundation to study the roles of astrocytes in epilepsy.
There are over three million Americans with epilepsy, and for nearly one-third of them, current treatments are ineffective. Amongst the epilepsies that are difficult to treat are temporal lobe epilepsy (TLE) and viral-induced epilepsy. This is in part because the development of these types of epilepsies is not well understood.
Evidence suggests that astrocytes – long dismissed by scientists as passive support cells for neurons – undergo dramatic changes when TLE and viral-induced epilepsies are triggered in animal models. White and Wilcox will research how astrocyte dynamics influence the development of TLE and infection-induced epilepsies.
“We think that our work may identify the heretofore ignored role that astrocytes may play in the pathology of epilepsy,” said White. “Such a discovery would naturally lead to new drug targets.”
The topic is relatively unexplored because it has been challenging to observe behaviors of astrocytes, which reside deep within neural networks, in real-time. These qualities are essential for documenting the play-by-play action of astrocytes from seizure induction to seizure manifestation.
It has taken collaboration between scientists in three disciplines – bioengineering, pharmacology, and genetics – to devise ways in which to approach this seemingly intractable problem. For example, White’s group developed a novel imaging technique, targeted path scanning 2-photon microscopy (TPS), which can monitor activity in networks of neurons and astrocytes at unprecedented speeds.
“We all bring considerable expertise to the table and that turns out to be key for developing innovative new tools that will help us understand the complex role of astrocytes in the development of different forms of acquired epilepsy,” said Wilcox.
Receiving the two grants is the culmination of a successful history of concentrated efforts by these scientists to create and test the tools and techniques to carry out this work. In 2009, White and Wilcox won a Challenge Grant in federal economic stimulus money to develop ways to visualize calcium signaling in astrocytes in vivo. In 2010, the two investigators, along with Petr Tvrdik and Mario Capecchi, were recipients of a University of Utah seed grant that helped to advance imaging tools.
“We have benefitted tremendously from the efforts of the Brain Institute, which has provided considerable support in helping us to identify funding sources, preparing grant applications, and navigating administrative hurdles to insure a seamless collaboration,” said Wilcox. “They have given us the opportunity to focus on the science at hand while helping us to garner the resources that will make new developments in epilepsy research a reality.”
The multidisciplinary project has the potential to lead to entirely new ways of identifying novel pharmacological therapies for preventing and treating TLE and viral-induced epilepsy.
- In September, 2012, Co-PIs John White, Ph.D. and Karen Wilcox, Ph.D. were awarded a five-year RO1 for $1,721,470 total from the NIH- National Institute of Neurological Disorders and Stroke for “Calcium Signaling in a Model of Temporal Lobe Epilepsy”.
- In October, 2012, Co- PIs John White, Ph.D. and Karen Wilcox, Ph.D. received a three-year grant for $300,000 total from the Ben B. and Iris M. Margolis Foundation for “Transgenic Mice for the Study of Infection-Induced Epilepsy.”
Astrocyte dynamics captured by targeted path scanning 2-photon microscopy (TPS)