Persistent ∆FosB expression limits recurrent seizure activity and provides neuroprotection in the dentate gyrus of APP mice.

Autor: Stephens GS; Department of Neuroscience, Baylor College of Medicine, USA., Park J; Department of Neuroscience, Baylor College of Medicine, USA., Eagle A; Department of Physiology, Michigan State University, USA., You J; Department of Neuroscience, Baylor College of Medicine, USA., Silva-Pérez M; Department of Neuroscience, Baylor College of Medicine, USA., Fu CH; Department of Neuroscience, Baylor College of Medicine, USA., Choi S; Department of Neuroscience, Baylor College of Medicine, USA., Romain CPS; Department of Neuroscience, Baylor College of Medicine, USA., Sugimoto C; Department of Physiology, Michigan State University, USA., Buffington SA; Center for Precision Environmental Health, Department of Neuroscience, Baylor College of Medicine, USA., Zheng Y; Department of Neuroscience, Baylor College of Medicine, USA., Costa-Mattioli M; Department of Neuroscience, Baylor College of Medicine, USA., Liu Y; Department of Neurobiology and Anatomy, McGovern Medical School at UT Health, USA., Robison AJ; Department of Physiology, Michigan State University, USA., Chin J; Department of Neuroscience, Baylor College of Medicine, USA. Electronic address: Jeannie.Chin@bcm.edu.
Jazyk: angličtina
Zdroj: Progress in neurobiology [Prog Neurobiol] 2024 Jun; Vol. 237, pp. 102612. Date of Electronic Publication: 2024 Apr 19.
DOI: 10.1016/j.pneurobio.2024.102612
Abstrakt: Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection to dentate granule cells, indicating that ∆FosB may act over long timescales to coordinate neuroprotective pathways. To test this hypothesis, we used viral-mediated expression of ∆JunD to interfere with ∆FosB signaling over the course of several months in transgenic mice expressing mutant human amyloid precursor protein (APP), which exhibit spontaneous seizures and develop AD-related neuropathology and cognitive deficits. Our results demonstrate that persistent ∆FosB activity acts through discrete modes of hippocampal target gene regulation to modulate neuronal excitability, limit recurrent seizure activity, and provide neuroprotection to hippocampal dentate granule cells in APP mice.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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