Cargando…

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

BACKGROUND: The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilo...

Descripción completa

Detalles Bibliográficos
Autores principales: Dickey, Chad A, Gordon, Marcia N, Wilcock, Donna M, Herber, Donna L, Freeman, Melissa J, Morgan, Dave
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549198/
https://www.ncbi.nlm.nih.gov/pubmed/15689237
http://dx.doi.org/10.1186/1471-2202-6-7
_version_ 1782122401653325824
author Dickey, Chad A
Gordon, Marcia N
Wilcock, Donna M
Herber, Donna L
Freeman, Melissa J
Morgan, Dave
author_facet Dickey, Chad A
Gordon, Marcia N
Wilcock, Donna M
Herber, Donna L
Freeman, Melissa J
Morgan, Dave
author_sort Dickey, Chad A
collection PubMed
description BACKGROUND: The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss. RESULTS: We report that in addition to decreased mRNA expression, there was decreased overall Na+/K+ ATPase enzyme activity in the amyloid-containing hippocampi of the APP+PS1 mice (although not in the amyloid-free cerebellum). In addition, dual immunolabeling revealed an absence of Na+/K+ ATPase staining in a zone surrounding congophilic plaques that was occupied by dystrophic neurites. We also demonstrate that cerebral Na+/K+ ATPase activity can be directly inhibited by high concentrations of soluble Aβ. CONCLUSIONS: The data suggest that the reductions in Na+/K+ ATPase activity in Alzheimer tissue may not be purely secondary to neuronal loss, but may results from direct effects of amyloid on this enzyme. This disruption of ion homeostasis and osmotic balance may interfere with normal electrotonic properties of dendrites, blocking intraneuronal signal processing, and contribute to neuritic dystrophia. These results suggest that therapies aimed at enhancing Na+/K+ ATPase activity in AD may improve symptoms and/or delay disease progression.
format Text
id pubmed-549198
institution National Center for Biotechnology Information
language English
publishDate 2005
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-5491982005-02-23 Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice Dickey, Chad A Gordon, Marcia N Wilcock, Donna M Herber, Donna L Freeman, Melissa J Morgan, Dave BMC Neurosci Research Article BACKGROUND: The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss. RESULTS: We report that in addition to decreased mRNA expression, there was decreased overall Na+/K+ ATPase enzyme activity in the amyloid-containing hippocampi of the APP+PS1 mice (although not in the amyloid-free cerebellum). In addition, dual immunolabeling revealed an absence of Na+/K+ ATPase staining in a zone surrounding congophilic plaques that was occupied by dystrophic neurites. We also demonstrate that cerebral Na+/K+ ATPase activity can be directly inhibited by high concentrations of soluble Aβ. CONCLUSIONS: The data suggest that the reductions in Na+/K+ ATPase activity in Alzheimer tissue may not be purely secondary to neuronal loss, but may results from direct effects of amyloid on this enzyme. This disruption of ion homeostasis and osmotic balance may interfere with normal electrotonic properties of dendrites, blocking intraneuronal signal processing, and contribute to neuritic dystrophia. These results suggest that therapies aimed at enhancing Na+/K+ ATPase activity in AD may improve symptoms and/or delay disease progression. BioMed Central 2005-02-02 /pmc/articles/PMC549198/ /pubmed/15689237 http://dx.doi.org/10.1186/1471-2202-6-7 Text en Copyright © 2005 Dickey et al; licensee BioMed Central Ltd.
spellingShingle Research Article
Dickey, Chad A
Gordon, Marcia N
Wilcock, Donna M
Herber, Donna L
Freeman, Melissa J
Morgan, Dave
Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice
title Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice
title_full Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice
title_fullStr Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice
title_full_unstemmed Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice
title_short Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice
title_sort dysregulation of na+/k+ atpase by amyloid in app+ps1 transgenic mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549198/
https://www.ncbi.nlm.nih.gov/pubmed/15689237
http://dx.doi.org/10.1186/1471-2202-6-7
work_keys_str_mv AT dickeychada dysregulationofnakatpasebyamyloidinappps1transgenicmice
AT gordonmarcian dysregulationofnakatpasebyamyloidinappps1transgenicmice
AT wilcockdonnam dysregulationofnakatpasebyamyloidinappps1transgenicmice
AT herberdonnal dysregulationofnakatpasebyamyloidinappps1transgenicmice
AT freemanmelissaj dysregulationofnakatpasebyamyloidinappps1transgenicmice
AT morgandave dysregulationofnakatpasebyamyloidinappps1transgenicmice