期刊
ENEURO
卷 8, 期 2, 页码 -出版社
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0345-20.2020
关键词
Angelman syndrome; epilepsy; epileptiform activity; quantitative EEG; seizures; spectral power
资金
- Foundation for Angelman Syndrome Therapeutics
- National Institute of Neurological Disorders and Stroke Brain Disorders and Development Training Grant [T32NS043124-07]
- American Epilepsy Society
- Pediatric Epilepsy Research Foundation
- Jan and Dan Duncan Neurological Research Institute Zoghbi Scholar Award
The maternal deletion of Ube3a in rats was found to result in epileptiform activity and significantly increased delta power in EEG, confirming the validity of this model in replicating some clinical aspects of Angelman syndrome.
Angelman syndrome (AS) is a neurodevelopmental disorder with unique behavioral phenotypes, seizures, and distinctive electroencephalographic (EEG) patterns. Recent studies identified motor, social communication, and learning and memory deficits in a CRISPR engineered rat model with a complete maternal deletion of the Ube3a gene. It is unknown whether this model recapitulates other aspects of the clinical disorder. We report here the effect of Ube3a maternal deletion in the rat on epileptiform activity, seizure threshold, and quantitative EEG. Using video-synchronized EEG (vEEG) monitoring, we assessed spectral power and epileptiform activity early postnatally through adulthood. While EEG power was similar to wild-type (WT) at 1.5 weeks postnatally, at all other ages analyzed, our findings were similar to the AS phenotype in mice and humans with significantly increased delta power. Analysis of epileptiform activity in juvenile and adult rats showed increased time spent in epileptiform activity in AS compared with WT rats. We evaluated seizure threshold using pentylenetetrazol (PTZ), audiogenic stimulus, and hyperthermia to provoke febrile seizures (FSs). Behavioral seizure scoring following PTZ induction revealed no difference in seizure threshold in AS rats, however behavioral recovery from the PTZ-induced seizure was longer in the adult group with significantly increased hippocampal epileptiform activity during this phase. When exposed to hyperthermia, AS rat pups showed a significantly lower temperature threshold to first seizure than WT. Our findings highlight an age-dependence for the EEG and epileptiform phenotypes in a preclinical model of AS, and support the use of quantitative EEG and increased delta power as a potential biomarker of AS.
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