title: The expression and activity of KV3.4 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 KV3.4 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 KV3.4 potassium channel subunits in astrocytes. In primary astrocytes our biochemical, immunohistochemical, and electrophysiological studies demonstrated a time-dependent upregulation of KV3.4 expression and functional activity after exposure to amyloid-β (Aβ) oligomers. Consistently, astrocytic KV3.4 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, KV3.4 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 KV3.4 subunits, but not Aβ. More important, we evidenced that the selective knockdown of KV3.4 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 KV3.4 channel subunits are precociously upregulated in cultured astrocytes exposed to Aβ oligomers and in reactive astrocytes of AD Tg2576 mice.
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Boscia
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pannaccione
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Roselia
authors.initials: R
authors.lastname: Ciccone
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Casamassa
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Franco
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Piccialli
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: de Rosa
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vinciguerra
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Di Renzo
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, "Federico II" University of Naples, Naples, Italy; Fondazione IRCCS SDN, Naples, Italy. Electronic address: lannunzi@unina.it.
authors.forename: Lucio
authors.initials: L
authors.lastname: Annunziato
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000009:adverse effects / Q000378:metabolism; D017208:Rats, Wistar; D051670:Shaw Potassium Channels / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; C115399:Kcnc4 protein, mouse; D010446:Peptide Fragments; D051670:Shaw Potassium Channels; C075222:amyloid beta-protein (1-42); C528900:glial fibrillary astrocytic protein, mouse
keywords: Alzheimer's disease; Astrocyte; Aβ(1-42); Aβ-oligomers; GFAP; K(V)3.4 potassium channel; Tg2576