Prior epigenetic status predicts future susceptibility to seizures in mice
Boros, B. D.; Gachechiladze, M. A.; Guo, J.; Galloway, D. A.; Mueller, S. M.; Shabsovich, M.; Yen, A.; Cammack, A. J.; Shen, T.; Mitra, R. D.; Dougherty, J. D.; Miller, T. M.
Show abstract
Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic epigenetic variation during neurodevelopment can mediate such phenotypic differences. However , this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development, and thereby associate epigenetic variation with a subsequent phenotypic presentation - degree of seizure response to the pro-convulsant pentylenetetrazol. We show that recorded differences in epigenetics at 243 loci predict a severe vs. mild response, and that these are enriched near genes associated with human epilepsy. We also validated pharmacologically a seizure -modifying role for two novel genes, Htr1f and Let7c. This proof-of-principle supports using CC broadly to discover predisposition loci for other neuropsychiatric traits and behaviors. Finally, as, human disease is also influenced by non-inherited factors, similar epigenetic predispositions are possible in humans.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Prefrontal PV interneurons facilitate attention and are linked to attentional dysfunction in a mouse model of absence epilepsy 96%
- Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome 96%
- Seizures, behavioral deficits and adverse drug responses in two new genetic mouse models of HCN1 epileptic encephalopathy 96%
Similar papers in this journal
- Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy 95%
- Developmentally-regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome 94%
- Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits 94%
Similar papers in this journal
- Genetic expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy 95%
- Kcnq2/Kv7.2 controls the threshold and bihemispheric symmetry of cortical spreading depolarization 95%
- Excitatory GABAergic signalling is associated with acquired benzodiazepine resistance in status epilepticus 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.