title: Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease.
abstract: In neurons, voltage-dependent Kv3 potassium channels are essential for the generation of action potentials at high frequency. A dysregulation of the Kv3.1 and Kv3.4 channel subunits has been suggested to contribute to neuronal and glial alterations in Alzheimer's disease, but a quantitative evaluation of these subunits in a mouse model of the pathology is still lacking. We analysed the profile of expression of the four Kv3 subunits by quantitative reverse transcription PCR and Western blot in the whole mouse brain and in dissected brain regions (olfactory bulb, septum, neocortex, hippocampus, brainstem and cerebellum) from 14 days after conception to 18 months after birth. In addition, we measured the levels of Kv3.1 and Kv3.4 messenger RNAs (mRNAs) and proteins in neocortex and hippocampus of APPPS1 mice, a transgenic model of Alzheimer's disease. Although all Kv3 transcripts were significantly expressed in embryonic age in whole brain extracts, only Kv3.1, Kv3.2 and Kv3.4 subunit proteins were present, suggesting a novel role for Kv3 channels at this developmental stage. With the exception of Kv3.4, during postnatal development, Kv3 transcripts and proteins showed a progressive increase in expression and reached an asymptote in adulthood, suggesting that the increase in Kv3 expression during development might contribute to the maturation of the electrical activity of neurons. During aging, Kv3 expression was rather stable. In contrast, in the neocortex of aged APPPS1 mice, Kv3.1 mRNA and protein levels were significantly lower compared to wild type, suggesting that a decrease in Kv3 currents could play a role in the cognitive symptoms of Alzheimer's disease.
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole, 10, Orbassano, 10043, Turin, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Boda
authors.forename: Eriola
authors.initials: E
authors.lastname: Hoxha
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.forename: Francesca
authors.initials: F
authors.lastname: Montarolo
authors.forename: Filippo
authors.initials: F
authors.lastname: Tempia
mesh_terms: D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D051670:Shaw Potassium Channels / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C489597:KCNC1 protein, human; C489596:KCNC2 protein, human; C489594:KCNC3 protein, human; C492015:KCNC4 protein, human; C490839:Kcnc1 protein, mouse; C085724:Kcnc3 protein, mouse; C115399:Kcnc4 protein, mouse; D051670:Shaw Potassium Channels