Hippocampal deletion of Na V 1.1 channels in mice causes thermal seizures and cognitive deficit characteristic of Dravet Syndrome
Year: 2019
Type: article
Abstract: Significance Dravet Syndrome is an intractable epileptic disorder that includes cognitive and social-interaction deficits. It is caused by loss-of-function mutations in the brain sodium channel Na V 1.1. We asked whether symptoms of Dravet Syndrome could be induced by introducing the mutation only in the hippocampus, a brain region important for learning and memory and for control of brain excitability. Local mutation of Na V 1.1 specifically reduced the excitability of inhibitory neurons in the hippocampus. This local mutation caused thermally evoked seizures and spatial learning deficits, which are brain-wide effects. Our results point to a key role for the hippocampus in generating epilepsy and cognitive deficit in Dravet Syndrome and suggest that gene therapy targeting the hippocampus might be effective in this devastating disease.
Institution: University of Washington
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2963561896