0000000000320019
AUTHOR
R. Maarten Van Dijk
Proteomic signature of the Dravet syndrome in the genetic Scn1a-A1783V mouse model.
Abstract Background Dravet syndrome is a rare, severe pediatric epileptic encephalopathy associated with intellectual and motor disabilities. Proteomic profiling in a mouse model of Dravet syndrome can provide information about the molecular consequences of the genetic deficiency and about pathophysiological mechanisms developing during the disease course. Methods A knock-in mouse model of Dravet syndrome with Scn1a haploinsufficiency was used for whole proteome, seizure, and behavioral analysis. Hippocampal tissue was dissected from two- (prior to epilepsy manifestation) and four- (following epilepsy manifestation) week-old male mice and analyzed using LC-MS/MS with label-free quantificati…
Proteomic signature of the Dravet syndrome in the genetic Scn1a-A1783V mouse model
AbstractBackgroundDravet syndrome is a rare, severe pediatric epileptic encephalopathy associated with intellectual and motor disabilities. Proteomic profiling in a mouse model of Dravet syndrome can provide information about the molecular consequences of the genetic deficiency and about pathophysiological mechanisms developing during the disease course.MethodsA knock-in mouse model of Dravet syndrome with Scn1a haploinsufficiency was used for whole proteome, seizure and behavioral analysis. Hippocampal tissue was dissected from two-(prior to epilepsy manifestation) and four-(following epilepsy manifestation) week-old male mice and analyzed using LC-MS/MS with label-free quantification. Pro…
Imaging correlates of behavioral impairments: An experimental PET study in the rat pilocarpine epilepsy model
Abstract Psychiatric comorbidities are prevalent in patients with epilepsy and greatly contribute to the overall burden of disease. The availability of reliable biomarkers to diagnose epilepsy-associated comorbidities would allow for effective treatment and improved disease management. Due to their non-invasive nature, molecular imaging techniques such as positron emission tomography (PET) are ideal tools to measure pathologic changes. In the current study we investigated the potential of [18F]fluoro-2-deoxy- d -glucose ([18F]FDG) and 2′-methoxyphenyl-(N-2′-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine ([18F]MPPF) as imaging correlates of neurobehavioral comorbidities in the pilocarpine …
Imaging biomarkers of behavioral impairments: A pilot micro-positron emission tomographic study in a rat electrical post-status epilepticus model.
Objective In patients with epilepsy, psychiatric comorbidities can significantly affect the disease course and quality of life. Detecting and recognizing these comorbidities is central in determining an optimal treatment plan. One promising tool in detecting biomarkers for psychiatric comorbidities in epilepsy is positron emission tomography (PET). Methods Results Behavioral and biochemical variables were cross-correlated with the results from two mu PET scans using the tracers [F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG) and 2 '-methoxyphenyl-(N-2 '-pyridinyl)-p-F-18-fluoro-benzamidoethylpiperazine ([F-18]MPPF) to explore potential biomarkers for neurobehavioral comorbidities in an electrica…
Toward evidence-based severity assessment in rat models with repeated seizures: I. Electrical kindling
Objective: Rodent epilepsy models can significantly contribute to our understanding of pathophysiological mechanisms and to validation of biomarker and target candidates. Evidence-based severity assessment is a presupposition for the ethical evaluation of animal experimentation allowances as well as for the development of efficacious refinement concepts. Methods: Aiming to improve our understanding of the impact of experimental procedures and repeated seizures, we have completed a comprehensive behavioral and biochemical analysis assessing various parameters that can inform about the influence of an electrical kindling paradigm on well-being in rats. Thereby, we have focused on the immediat…