Journal
NEUROCHEMICAL RESEARCH
Volume 43, Issue 4, Pages 878-885Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-018-2493-z
Keywords
Axon initial segment; Cortical dysplasia; Nifedipine; Seizure susceptibility; Structural plasticity
Categories
Funding
- Natural Science Foundation of China [81000553, 81771407]
Ask authors/readers for more resources
Cortical dysplasia is the most common etiology of intractable epilepsy. Both excitability changes in cortical neurons and neural network reconstitution play a role in cortical dysplasia epileptogenesis. Recent research shows that the axon initial segment, a subcompartment of the neuron important to the shaping of action potentials, adjusts its position in response to changes in input, which contributes to neuronal excitability and local circuit balance. It is unknown whether axon initial segment plasticity occurs in neurons involved in seizure susceptibility in cortical dysplasia. Here, we developed a Carmustine- pilocarpine rat model of cortical dysplasia and show that it exhibits a lower seizure threshold, as indicated by behavior studies and electroencephalogram monitoring. Using immunofluorescence, we measured the axon initial segment positions of deep L5 somatosensory neurons and show that it is positioned closer to the soma after acute seizure, and that this displacement is sustained in the chronic phase. We then show that Nifedipine has a dose-dependent protective effect against axon initial segment displacement and increased seizure susceptibility. These findings further our understanding of the pathophysiology of seizures in cortical dysplasia and suggests Nifedipine as a potential therapeutic agent.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available