Epilepsy is a prevalent neurological disorder. Nonetheless, many patients are considered treatment-resistant. Therefore, there is an urgent need to understand the pathophysiology of treatment-resistant epilepsy and to develop improved medications. Hippocampal inhibitory interneurons (INs) supply the local inhibitory tone and are key players in epileptic seizures and their activity can control refractory seizures.
This project will focus on Neurensin-2, which is selectively expressed in hippocampal INs and induces INs activity, thus, has a potential to alleviate refractory epilepsy. Indeed, human data indicates that genetic abnormalities in the Neurensin-2 coding region are associated with treatment-resistant epilepsy. Nonetheless, the direct effects of Neurensin-2 on seizures are unknown. In this study, we will examine the potential of Neurensin-2 as a novel cell-type-specific anti-epileptic protein. We will combine knowledge from two labs with expertise in epilepsy and Neurensin-2 research. We will use unique tools, including Neurensin-2 knockout mice and viral constructs, to modulate Neurensin-2 expression.
Then, we will examine the effect of Neurensin-2 on evoked seizures. Thus, this project will provide proof of concept that Neurensin-2 is a novel seizure modulator. These data will pave the path for extensive research that will focus on Neurensin-2 in epilepsy and its future treatments.