Neurosteroids reverse tonic inhibitory deficits in Fragile X syndrome mouse model
Abstract
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. In addition, there is increased incidence of anxiety, sleep irregularities, and seizure activity. The underlying cause of FXS is a loss of the fragile X mental retardation protein (FMRP) which has been shown to participate in the biosynthesis of δ subunits. Studies from both FXS patients and animal models have revealed reduced expression levels of GABAAR α4 and δ subunits with a reduced efficacy of tonic inhibition. Neurosteroids (NS) are known allosteric modulators of GABAAR channel function but recent studies from our laboratory have revealed that NS also exert persistent effects on the efficacy of tonic inhibition by increasing the PKC‐mediated phosphorylation of the α4 subunit which increases the membrane expression and boosts tonic inhibition. We have used a combination of biochemical and electrophysiological methods to assess alterations in GABAergic signaling in the hippocampus of FMRP knock‐out mouse (Fmr1 KO), a widely validated model of the human syndrome.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2017
- Source ID
- 10.1096/fasebj.31.1_supplement.815.12
Entities
People
- Amit A Modgil
- James Doherty
- Manasa Parakala
- Mike Ackley
- Paul A. Davies
- Stephen J. Moss
Organizations
- Simons Foundation
- Tufts University
- United States Department of Defense