Store depletion-induced h-channel plasticity rescues a channelopathy linked to Alzheimer's disease.

Autor: Musial TF; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Molina-Campos E; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Bean LA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Ybarra N; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Borenstein R; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Russo ML; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Buss EW; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Justus D; Neuronal Networks Group, Deutsches Zenstrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany., Neuman KM; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Ayala GD; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Mullen SA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Voskobiynyk Y; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Tulisiak CT; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Fels JA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Corbett NJ; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Carballo G; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Kennedy CD; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Popovic J; Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Ramos-Franco J; Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612, USA., Fill M; Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612, USA., Pergande MR; Department of Pathology, Rush University Medical Center, Chicago, IL 60612, USA., Borgia JA; Department of Pathology, Rush University Medical Center, Chicago, IL 60612, USA; Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA., Corbett GT; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Pahan K; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA., Han Y; Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Chetkovich DM; Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Vassar RJ; Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Byrne RW; Department of Neurosurgery, Rush University Medical Center, Chicago, IL 60612, USA., Matthew Oh M; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Stoub TR; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA; Department of Neurosurgery, Rush University Medical Center, Chicago, IL 60612, USA., Remy S; Neuronal Networks Group, Deutsches Zenstrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany; Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Straβe 25, 53125 Bonn, Germany., Disterhoft JF; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: jdisterhoft@northwestern.edu., Nicholson DA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: dan_nicholson@rush.edu.
Jazyk: angličtina
Zdroj: Neurobiology of learning and memory [Neurobiol Learn Mem] 2018 Oct; Vol. 154, pp. 141-157. Date of Electronic Publication: 2018 Jun 12.
DOI: 10.1016/j.nlm.2018.06.004
Abstrakt: Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however, are misregulated in several neurological disorders, causing both gain- and loss-of-function channelopathies in neurons. Using several transgenic mouse models of Alzheimer's disease (AD), we find that sub-threshold voltage signals strongly influenced by hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels progressively deteriorate over chronological aging in hippocampal CA1 pyramidal neurons. The degraded signaling via HCN channels in the transgenic mice is accompanied by an age-related global loss of their non-uniform dendritic expression. Both the aberrant signaling via HCN channels and their mislocalization could be restored using a variety of pharmacological agents that target the endoplasmic reticulum (ER). Our rescue of the HCN channelopathy helps provide molecular details into the favorable outcomes of ER-targeting drugs on the pathogenesis and synaptic/cognitive deficits in AD mouse models, and implies that they might have beneficial effects on neurological disorders linked to HCN channelopathies.
(Copyright © 2018. Published by Elsevier Inc.)
Databáze: MEDLINE
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