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Prolonged Aβ treatment leads to impairment in the ability of primary cortical neurons to maintain K+ and Ca²+ homeostasis

Citation

Shabala, L and Howells, C and West, AK and Chung, RS, Prolonged Aβ treatment leads to impairment in the ability of primary cortical neurons to maintain K+ and Ca + homeostasis, Molecular Neurodegeneration, 5, (30) EJ ISSN 1750-1326 (2010) [Refereed Article]


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Copyright Statement

© 2010 Shabala et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: doi:10.1186/1750-1326-5-30

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease, characterised by the formation of insoluble amyloidogenic plaques and neurofibrillary tangles. Beta amyloid (Ab) peptide is one of the main constituents in Ab plaques, and is thought to be a primary causative agent in AD. Neurons are likely to be exposed to chronic, sublethal doses of Ab over an extended time during the pathogenesis of AD, however most studies published to date using in vitro models have focussed on acute studies. To experimentally model the progressive pathogenesis of AD, we exposed primary cortical neurons daily to 1 !M of Ab1-40 over 7 days and compared their survival with age-similar untreated cells. We also investigated whether chronic Ab exposure affects neuronal susceptibility to the subsequent acute excitotoxicity induced by 10 !M glutamate and assessed how Ca2+ and K+ homeostasis were affected by either treatment. Results: We show that continuous exposure to 1 !M Ab1-40 for seven days decreased survival of cultured cortical neurons by 20%. This decrease in survival correlated with increased K+ efflux from the cells. One day treatment with 1 !M Ab followed by glutamate led to a substantially higher K+ efflux than in the age-similar untreated control. This difference further increased with the duration of the treatment. K+ efflux also remained higher in Ab treated cells 20 min after glutamate application leading to 2.8-fold higher total K+ effluxed from the cells compared to controls. Ca2+ uptake was significantly higher only after prolonged Ab treatment with 2.5-fold increase in total Ca2+ uptake over 20 min post glutamate application after six days of Ab treatment or longer (P < 0.05). Conclusions: Our data suggest that long term exposure to Ab is detrimental because it reduces the ability of cortical neurons to maintain K+ and Ca2+ homeostasis in response to glutamate challenge, a response that might underlie the early symptoms of AD. The observed inability to maintain K+ homeostasis might furthermore be useful in future studies as an early indicator of pathological changes in response to Ab.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Shabala, L (Dr Lana Shabala)
Author:Howells, C (Ms Claire Howells)
Author:West, AK (Professor Adrian West)
Author:Chung, RS (Associate Professor Roger Chung)
ID Code:65192
Year Published:2010
Web of Science® Times Cited:10
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-10-13
Last Modified:2011-05-02
Downloads:416 View Download Statistics

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