Authors

Brian F Corbett, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PAFollow
Jason C You, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Xiaohong Zhang, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Mark S Pyfer, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Umberto Tosi, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Daniel M Iascone, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Iraklis Petrof, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Anupam Hazra, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Chia-Hsuan Fu, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA; Department of Neuroscience, Baylor College of Medicine, Houston, TX
Gabriel S Stephens, Department of Neuroscience, Baylor College of Medicine, Houston, TX
Annie Ashok, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PAFollow
Suzan Aschmies, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA
Lijuan Zhao, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PAFollow
Eric J Nestler, Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Jeannie Chin, Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; Department of Neuroscience, Baylor College of Medicine, Houston, TXFollow

Document Type

Article

Publication Date

7-11-2017

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

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.

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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