Document Type
Article
Publication Date
7-11-2017
Abstract
Alzheimer's disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in ΔFosB-mediated suppression of c-Fos, suggesting that this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits, even during seizure-free periods.
Recommended Citation
Corbett, Brian F; You, Jason C; Zhang, Xiaohong; Pyfer, Mark S; Tosi, Umberto; Iascone, Daniel M; Petrof, Iraklis; Hazra, Anupam; Fu, Chia-Hsuan; Stephens, Gabriel S; Ashok, Annie; Aschmies, Suzan; Zhao, Lijuan; Nestler, Eric J; and Chin, Jeannie, "ΔFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer's Disease." (2017). Department of Neuroscience Faculty Papers. Paper 27.
https://jdc.jefferson.edu/department_neuroscience/27
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
This article has been peer reviewed. It was published in: Cell Reports.
Volume 20, Issue 2, 11 July 2017, Pages 344-355.
The published version is available at DOI: 10.1016/j.celrep.2017.06.040
Copyright © 2017 The Authors