Voltage-Gated Ion Channel Dysfunction in Tuberous Sclerosis

Abstract

Tuberous sclerosis is a single gene disorder that affects the function of multiple organ systems including the brain. Patients with tuberous sclerosis may experience neurodevelopmental delay, epilepsy, and neuropsychiatric disorders such as cognitive disability and autism spectrum disorder. Voltage-gated ion channels are critical to the neuron function particularly as regulators of cell excitability. Given that cell and circuit hyperexcitability is an established characteristic of tuberous sclerosis, it is surprising that there are few studies of tuberous sclerosis that investigate changes in voltage-gated ion channels. We suggest the intriguing possibility that changes in the function of voltage-gated ion channels contribute to brain circuit deficits in tuberous sclerosis. Given that there are many currently approved pharmaceutical agents that target specific voltage-gated ion channels, the insights gained from this proposal may identify novel therapeutic targets in the treatment of tuberous sclerosis. This proposal is thus highly relevant to the Tuberous Sclerosis Complex Research Program and addresses two of the Hypothesis Development Award Focus Areas: (1) preventing epilepsy, improving treatment, and mitigating neurodevelopmental outcomes associated with TSC-related seizures and (2) understanding the features of TSC-Associated Neuropsychiatric Disorders and reducing their impact, including pharmacological and behavioral interventions.

Document Details

Document Type
DoD Grant Award
Publication Date
Dec 28, 2022
Source ID
W81XWH2210260

Entities

People

  • Darrin Brager

Organizations

  • United States Army
  • University of Texas at Austin

Tags

Fields of Study

  • Medicine
  • Psychology

Readers

  • Aquatic Ecology
  • Neuroscience
  • Neurotrauma and Rehabilitation Medicine.