NYMC Student Theses and Dissertations
Date of Award
12-1-2022
Document Type
Doctoral Dissertation - Restricted (NYMC/Touro only) Access
Degree Name
Doctor of Philosophy
Department
Cell Biology
First Advisor
Eliana Scemes, PhD
Abstract
Epileptic seizures result from central nervous system (CNS) hyperexcitation due to imbalances in excitatory and inhibitory signaling. Purinergic signals mediated by extracellular adenosine triphosphate (ATP) can exacerbate seizures by augmenting CNS excitatory tone and thus tip the excitatory/inhibitory (E/I) balance toward hyperexcitation. The ATP-release channel, pannexin 1 (Panx1), is found in neurons and astrocytes and contributes to neuroglial purinergic signaling. These channels play important roles in normal CNS physiology, but also have pathologic roles as Panx1’s activity is evidenced to contribute to CNS hyperexcitation and neuroinflammation. Panx1 participation in seizures leaves unanswered the question whether it has a role in the E/I imbalance identified in autism spectrum disorder (ASD), a syndrome highly associated with seizure disorders. Whether and how neuronal or astrocyte Panx1 contribute to hyperexcitation and seizure-induced comorbidities has never been investigated. Recent findings from our laboratory show that neuronal and astrocyte Panx1 contribute differently to hyperexcitation in the kainic acid (KA) model of seizure and epileptiform activity, namely in duration of events. And global deletion of Panx1 prevents changes that produce an autism-like phenotype following early-life seizures, specifically in social behavior. Our data suggest that these distinct effects of astrocyte and neuronal Panx1 result from differences in the magnitudes of ATP release from these two cell populations. The focus of this thesis is to dissect the mechanisms by which cell-specific Panx1 contributes to seizure/epileptiform activity and investigate the consequence of this hyperexcitation on behavior in the rodent model of KA-induced seizures. Findings from these studies increase the understanding of the relative contribution of neuronal Panx1 and glial Panx1 to seizures and reveal the importance of this channel to seizure-induced behavioral deficits.
Recommended Citation
Obot, Price, "Distinct Roles of Astrocyte and Neuronal Panx1 in Kainic Acid-Induced Seizures and Related Behavioral Deficits" (2022). NYMC Student Theses and Dissertations. 54.
https://touroscholar.touro.edu/nymc_students_theses/54
