Motor coordination and synaptic plasticity deficits are associated with increased cerebellar activity of NADPH oxidase, CAMKII, and PKC at preplaque stage in the TgCRND8 mouse model of Alzheimer's disease
Articolo
Data di Pubblicazione:
2018
Citazione:
Motor coordination and synaptic plasticity deficits are associated with increased cerebellar activity of NADPH oxidase, CAMKII, and PKC at preplaque stage in the TgCRND8 mouse model of Alzheimer's disease / R. Russo, F. Cattaneo, P. Lippiello, C. Cristiano, F. Zurlo, M. Castaldo, C. Irace, T. Borsello, R. Santamaria, R. Ammendola, A. Calignano, M.C. Miniaci. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - (2018 Mar 05). [Epub ahead of print] [10.1016/j.neurobiolaging.2018.02.025]
Abstract:
Numerous studies indicate that the cerebellum undergoes structural and functional neurodegenerative changes in Alzheimer's disease. The purpose of this study was to examine the extent of cerebellar alterations at early, preplaque stage of the pathology in TgCRND8 mice through behavioral, electrophysiological, and molecular analysis. Balance beam test and foot-printing analysis revealed significant motor coordination and balance deficits in 2-month-old TgCRND8 mice compared to their littermates. Patch-clamp recordings performed on cerebellar slices of transgenic mice showed synaptic plasticity deficit and loss of noradrenergic modulation at parallel fiber-Purkinje cell synapse suggesting an early dysfunction of the cerebellar circuitry due to amyloid precursor protein overexpression. Finally, western blot analysis revealed an enhanced expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p47phoxand p67phoxas well as Ca2+/calmodulin-dependent protein kinase and protein kinase C alpha in the cerebellum of 2-month-old transgenic mice. Therefore, we propose the existence of self-sustaining feedback loop involving the formyl peptide receptor 2-reactive oxygen species-Ca2+/calmodulin-dependent protein kinase II-protein kinase C alpha pathway that may promote reactive oxygen species generation in the early stage of Alzheimer's disease and eventually contribute to the exacerbation of pathological phenotype.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Alzheimer's disease; Noradrenaline; oxidative stress; patch-clamp recordings; synaptic plasticity; β-amyloid; neuroscience (all); aging; neurology (clinical); developmental biology; geriatrics and gerontology
Elenco autori:
R. Russo, F. Cattaneo, P. Lippiello, C. Cristiano, F. Zurlo, M. Castaldo, C. Irace, T. Borsello, R. Santamaria, R. Ammendola, A. Calignano, M.C. Miniaci
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