Electrophysiological alterations of pyramidal cells and interneurons of the CA1 region of the hippocampus in a novel mouse model of Dravet syndrome
In this paper, Dyment et al detail a new mouse for the study of Dravet syndrome modeled after a patient mutation. This particular mutation (H939R) does not result in the typical haploinsufficiency where Nav1.1 sodium channel levels are reduced, but rather appears to affect the function of one copy of the sodium channel. Consistent with other models of Dravet, these mice have spontaneous and heat-induced seizures, delayed growth, and increased mortality. Significant alterations in the electrical currents from hippocampal neurons indicate that sodium channels are not working properly in these mice carrying the H939R mutation. These mice also have reduced numbers of specific neuron populations, some of which have been reported in other models. However, they report for the first time a reduction in interneurons expressing vesicular acetylcholine transferase, implicating a potential role for acetylcholine in Dravet syndrome. The researchers also compared neurons derived from induced pluripotent stem cells from the original individual with Dravet and an unaffected individual, and found similar results in the electrical properties to those observed in the mouse model.
As discussed in other research reviews, there are now many mouse models of Dravet syndrome. Most of these models display a range of phenotypes, that can vary based on the type of mutation in the SCN1A gene and the strain of mouse, as well as the age and gender of the mice used in the studies. While a lot of variation in the results can make drawing conclusions a bit more difficult, it is also important to remember the amount of variability in the human population with Dravet, and recognize that exploring the different animal models of Dravet syndrome may help find treatments that work for broader patient populations.
Dr. Hood joined the DSF staff in 2020. She has an MS in Biology from East Tennessee State University and a PhD in Cell, Stem Cell, and Developmental Biology from the University of Colorado. She spent 10 years in laboratory settings researching how small changes in genetic and molecular regulation contribute to complex neurological diseases.
In 2007, Veronica had a son, Gabriel, who faced severe developmental challenges. Gabriel presented with initial seizure activity within his first two months of life, and his medical needs quickly became quite complex. Despite endless testing, a diagnosis remained elusive, and at the age of 8, Gabriel passed away. These experiences fueled Veronica’s passion to advance medical research and shaped her desire to support other families facing similar challenges. She hopes to apply her scientific knowledge and her understanding of the caregiver experience to support the Dravet community by facilitating Dravet-focused research and acting as a liaison between researchers, professionals, and families.