Abstract | OBJECTIVE: METHODS:
Pilocarpine chemoconvulsant was used to induce status epilepticus. To suppress CREB activity, a transgenic mouse line expressing an inducible dominant negative mutant of CREB (CREB(IR) ) with a serine to alanine 133 substitution was used. Status epilepticus and spontaneous seizures of transgenic and wild-type mice were analyzed using video-electroencephalography (EEG) to assess the effect of CREB suppression on seizures. RESULTS: Our findings indicate that activation of CREB(IR) shortens the duration of status epilepticus. The frequency of spontaneous seizures decreased in mice with chronic epilepsy during CREB(IR) induction; however, the duration of the spontaneous seizures was unchanged. Of interest, we found significantly reduced levels of phospho-CREB Ser133 upon activation of CREB(IR) , supporting prior work suggesting that binding to the CRE site is important for CREB phosphorylation. SIGNIFICANCE: Our results suggest that CRE transcription supports seizure activity both during status epilepticus and in spontaneous seizures. Thus, blocking of CRE transcription is a novel target for the treatment of epilepsy.
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Authors | Xinjian Zhu, Deepti Dubey, Camilo Bermudez, Brenda E Porter |
Journal | Epilepsia
(Epilepsia)
Vol. 56
Issue 12
Pg. 1870-8
(Dec 2015)
ISSN: 1528-1167 [Electronic] United States |
PMID | 26419901
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Wiley Periodicals, Inc. © 2015 International League Against Epilepsy. |
Chemical References |
- Convulsants
- Pilocarpine
- CREB-Binding Protein
- Crebbp protein, mouse
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Topics |
- Animals
- Brain Chemistry
- CREB-Binding Protein
(analysis, antagonists & inhibitors)
- Convulsants
(pharmacology)
- Disease Models, Animal
- Female
- Immunoblotting
- Male
- Mice
- Mice, Inbred C3H
- Mice, Inbred C57BL
- Mice, Transgenic
- Phosphorylation
- Pilocarpine
(pharmacology)
- Real-Time Polymerase Chain Reaction
- Seizures
(chemically induced, physiopathology)
- Status Epilepticus
(chemically induced, physiopathology)
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