The expression and activity of K V 3.4 channel subunits are precociously upregulated in astrocytes exposed to Aβ oligomers and in astrocytes of Alzheimer's disease Tg2576 mice
Abstract
Astrocyte dysfunction emerges early in Alzheimer's disease (AD) and may contribute to its pathology and progression. Recently, the voltage gated potassium channel K V 3.4 subunit, which underlies the fast-inactivating K+ currents, has been recognized to be relevant for AD pathogenesis and is emerging as a new target candidate for AD. In the present study, we investigated both in in vitro and in vivo models of AD the expression and functional activity of K V 3.4 potassium channel subunits in astrocytes. In primary astrocytes our biochemical, immunohistochemical, and electrophysiological studies demonstrated a time-dependent upregulation of K V 3.4 expression and functional activity after exposure to amyloid-β (Aβ) oligomers. Consistently, astrocytic K V 3.4 expression was upregulated in the cerebral cortex, hippocampus, and cerebellum of 6-month-old Tg2576 mice. Further, confocal triple labeling studies revealed that in 6-month-old Tg2576 mice, K V 3.4 was intensely coexpressed with Aβ in nonplaque associated astrocytes. Interestingly, in the cortical and hippocampal regions of 12-month-old Tg2576 mice, plaque-associated astrocytes much more intensely expressed K V 3.4 subunits, but not Aβ. More important, we evidenced that the selective knockdown of K V 3.4 expression significantly downregulated both glial fibrillary acidic protein levels and Aβ trimers in the brain of 6-month-old Tg2576 mice. Collectively, our results demonstrate that the expression and function of K V 3.4 channel subunits are precociously upregulated in cultured astrocytes exposed to Aβ oligomers and in reactive astrocytes of AD Tg2576 mice.
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Aβ-induced dysregulation of ionic homeostasis in astroglial cells may crucially contribute to their pathological remodelling.
“In turn, the Aβ-induced dysregulation of ionic homeostasis in astroglial cells may crucially contribute to their pathological remodelling (Boscia et al., 2017; Verkhratsky et al., 2017; Piccialli et al., 2020).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Boscia et al., 2017
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- Authors
- Boscia, F., Pannaccione, A., Ciccone, R., Casamassa, A., Franco, C., Piccialli, I., de Rosa, V., Vinciguerra, A., Di Renzo, G., & Annunziato, L.
- Affiliations
- University of Naples Federico II (IT)
- Corresponding author
- Annunziato, Lucio
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 54
- Pages
- 187-198
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2595111178
- Cited by
- 51
- References
- 45
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 7 · 2018: 1 · 2017: 1 · 2012: 1
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- voltage-gated potassium channels, astrocytes, Alzheimer's disease, amyloid-beta oligomers, Tg2576 mice, reactive astrocytes, amyloid plaques, glial fibrillary acidic protein, astrocyte dysfunction
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Brain, Cells, Cultured, Disease Models, Animal, Glial Fibrillary Acidic Protein, Male, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Up-Regulation, Gene Expression, Amyloid beta-Peptides, Rats, Wistar, Mice, Shaw Potassium Channels
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