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Store depletion-induced h-channel plasticity rescues a channelopathy linked to Alzheimer’s disease
- Source :
- Neurobiology of learning and memory 154, 141-157 (2018). doi:10.1016/j.nlm.2018.06.004
- Publication Year :
- 2018
-
Abstract
- Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however, are mis-regulated 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.
- Subjects :
- 0301 basic medicine
Male
Aging
physiopathology [Channelopathies]
Action Potentials
Hippocampal formation
Endoplasmic Reticulum
Behavioral Neuroscience
0302 clinical medicine
H channel
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Neuronal Plasticity
biology
physiology [Pyramidal Cells]
Chemistry
Pyramidal Cells
physiology [Endoplasmic Reticulum]
physiology [Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels]
Female
Genetically modified mouse
Cognitive Neuroscience
Experimental and Cognitive Psychology
Mice, Transgenic
TRIP8b
physiopathology [Alzheimer Disease]
Article
03 medical and health sciences
Channelopathy
Alzheimer Disease
ddc:570
medicine
HCN channel
Electron microscopy
Animals
Patch clamp
CA1 Region, Hippocampal
Ion channel
physiology [CA1 Region, Hippocampal]
Endoplasmic reticulum
ultrastructure [Pyramidal Cells]
ultrastructure [CA1 Region, Hippocampal]
medicine.disease
Disease Models, Animal
030104 developmental biology
Array tomography
biology.protein
Carvedilol
Channelopathies
Neuroscience
Patch-clamp
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Neurobiology of learning and memory 154, 141-157 (2018). doi:10.1016/j.nlm.2018.06.004
- Accession number :
- edsair.doi.dedup.....5edbb564e58b08463b6143441f802c0b
- Full Text :
- https://doi.org/10.1016/j.nlm.2018.06.004