A novel GABAergic dysfunction in human Dravet syndrome

(Ruffolo et al. 2018) Gamma-aminobutyric acid (GABA) is a small compound that acts on different receptors in the brain such as GABAA and GABAB and is considered one of the main inhibitory neurotransmittors. Dysfunction of the GABAergic system is found in many neurological disorders, and although mutations in genes that code for subunits of GABA receptors are sometimes found in patients with Dravet syndrome (such as GABRA1 and GABRG2), evidence of GABAergic dysfunction in Dravet syndrome is lacking.

In this study, the authors transplanted cell membranes (where GABA receptors and sodium ion channels are found) from human brain tissue of deceased patients with Dravet syndrome into frog oocytes (like eggs). By studying the human proteins in living cells (albeit non-human), the researchers hoped to more accurately approximate function. They also transplanted membranes from patients with tuberous sclerosis complex (TSC, a “control” of a neurodevelopmental disorder without SCN1A mutations) and healthy controls to determine what differences, if any, were unique to Dravet syndrome.

They found significant differences in GABAergic function between the patients with DS and the controls, as well as an improvement in GABAergic function when cannabidiol (CBD) was added to the TSC and DS cells, similar to the way benzodiazepines improved function in the cells. Together, this data suggests GABAergic dysfunction may play a role in DS and that GABAergic therapies may be an avenue for treatment.

Ruffolo G, Cifelli P, Roseti C, Thom M, van Vliet EA, Limatola C, Aronica E, Palma E. A novel GABAergic dysfunction in human Dravet syndrome. Epilepsia. 2018 Oct 11. doi: 10.1111/epi.14574. [Epub ahead of print] PubMed PMID: 30306542.
By |2018-10-13T12:05:18+00:00October 13th, 2018|Categories: DSF Research Review|Tags: |

About the Author:

Nicole is a former scientist and science educator who has an 11 year old son with Dravet syndrome and serves on the Board of Directors for the Dravet Syndrome Foundation. She reviews and summarizes research articles, making the content more accessible to those not involved in the scientific community.