Disordered breathing in a mouse model of Dravet syndrome
| Autor: | Xinnian Chen, Daniel K Mulkey, Fu-Shan Kuo, Colin M Cleary, Joseph J. LoTurco |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
SUDEP Mouse Action Potentials Epilepsies Myoclonic retrotrapezoid nucleus brainstem Mice Epilepsy 0302 clinical medicine Medicine Missense mutation Biology (General) Sudden Unexpected Death in Epilepsy Respiratory system Neurons SCN1a missense mutation chemoreception Respiration General Neuroscience Apnea General Medicine 3. Good health Hypoventilation Breathing medicine.symptom Research Article medicine.medical_specialty QH301-705.5 Science Mutation Missense General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Dravet syndrome Seizures Internal medicine Animals Humans General Immunology and Microbiology business.industry Carbon Dioxide medicine.disease NAV1.1 Voltage-Gated Sodium Channel Disease Models Animal 030104 developmental biology Endocrinology Respiratory failure business 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | eLife eLife, Vol 8 (2019) |
| ISSN: | 2050-084X |
| Popis: | Dravet syndrome (DS) is a form of epilepsy with a high incidence of sudden unexpected death in epilepsy (SUDEP). Respiratory failure is a leading cause of SUDEP, and DS patients’ frequently exhibit disordered breathing. Despite this, mechanisms underlying respiratory dysfunction in DS are unknown. We found that mice expressing a DS-associated Scn1a missense mutation (A1783V) conditionally in inhibitory neurons (Slc32a1cre/+::Scn1aA1783V fl/+; defined as Scn1aΔE26) exhibit spontaneous seizures, die prematurely and present a respiratory phenotype including hypoventilation, apnea, and a diminished ventilatory response to CO2. At the cellular level in the retrotrapezoid nucleus (RTN), we found inhibitory neurons expressing the Scn1a A1783V variant are less excitable, whereas glutamatergic chemosensitive RTN neurons, which are a key source of the CO2/H+-dependent drive to breathe, are hyper-excitable in slices from Scn1aΔE26 mice. These results show loss of Scn1a function can disrupt respiratory control at the cellular and whole animal levels. |
| Databáze: | OpenAIRE |
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