Role of kainate receptors on modulation of synaptic transmission and seizure susceptibility to hypoxia in neonatal mice
Gap funding award
Q: Please describe your project.
Seizures in neonates are a vexing clinical problem with lack of consensus on diagnosis and management. The problem is further compounded by the disappointing efficacy of currently available anti-seizure drugs. The lack of progress in improving treatment algorithms for these patients is partly due to an incomplete understanding of the mechanisms underlying seizure generation in an immature brain, particularly in the acute phase. Kainate receptors are highly expressed in the neonatal brain and their role in response to hypoxia and seizure generation in the developing brain is not clear. Our proposal explores the role of kainate receptors in modulating excitatory and inhibitory synaptic transmission as well as seizure generation in response to hypoxia in the neonatal mouse. This project will advance our understanding of the pathophysiology of neonatal seizures secondary to hypoxia in a novel direction.
Q: What does this funding mean to you and your research?
The Gap Funding Award will allow our team to explore a novel hypothesis that kainate receptors, which are highly expressed in the neonatal brain, play an important role in response to hypoxia and seizure generation in neonates. Because of this funding, we will be able to test our hypothesis and obtain critical preliminary data necessary for the submission of a larger grant.
Q: What is the most exciting part of your project so far?
While a large amount of research has focused on excitatory to inhibitory synaptic transmission imbalance, the knowledge gained in this area has failed to lead to more effective or safer therapies. The preliminary data we have obtained thus far suggest that kainate receptors play an important role in the pathophysiology of neonatal seizures. Understanding their exact role will be critical in identifying novel mechanisms-based therapeutic targets.
Q: What are you most excited about for the coming year?
We are excited to have the opportunity to better understand this novel hypothesis but mostly we are hopeful that this will lead to the development of safe and effective and therapeutic options for neonates suffering from early-life seizures. Intractable seizures are not an uncommon problem and have devastating consequences. It is only by understanding causes and effect that we will advance our ability to help these patients and their families.
Q: What else would you like to share?
We are very thankful to the School of Medicine for their support!