Perturbations in calcium-mediated signal transduction in microglia from Alzheimer's disease patients.

Abstract

Calcium-sensitive fluorescence microscopy has been used to study Ca2+-dependent signal transduction pathways in microglia obtained from Alzheimer's disease (AD) patients and non-demented (ND) individuals. Data were obtained from nine AD cases and seven ND individuals and included basal levels of intracellular Ca2+ [Ca2+]i, peak amplitudes (Delta[Ca2+]i) and time courses of adenosine triphosphate (ATP) responses and amplitudes of an initial transient response and a subsequent second component of Ca2+ influx through store-operated channels (SOC) induced by platelet-activating factor (PAF). Overall, AD microglia were characterized by significantly higher (20%) basal Ca2+ [Ca2+]i relative to ND cells. The Delta[Ca2+]i of ATP and initial phase of PAF responses, which reflect rapid depletion of Ca2+ from endoplasmic reticulum stores, were reduced by respective values of 63% and 59% in AD cells relative to amplitudes recorded from ND microglia. Additionally, AD microglia showed diminished amplitudes (reduction of 61%) of SOC-mediated Ca2+ entry induced by PAF and prolonged time courses (increase of 60%) of ATP responses with respect to ND microglia. We have generally replicated these results with exposure of human fetal microglia to beta amyloid (5 microM Abeta1-42 applied for 24 hr). Overall, these data indicate significant abnormalities are present in Ca2+-mediated signal transduction in microglia isolated from AD patients.

• Authors: James G McLarnon, Hyun B Choi, Lih-Fen Lue, Douglas G Walker, Seung U Kim
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 81 Issue 3 Pg. 426-35 (Aug 01 2005) ISSN: 0360-4012 [Print] United States
• PMID: 15948178 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: (c) 2005 Wiley-Liss, Inc.

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• Platelet Activating Factor
• amyloid beta-protein (1-42)
• Adenosine Triphosphate
• Calcium

Topics

• Adenosine Triphosphate (pharmacology)
• Alzheimer Disease (pathology)
• Amyloid beta-Peptides (pharmacology)
• Analysis of Variance
• Calcium (metabolism)
• Cells, Cultured
• Drug Interactions
• Fetus
• Humans
• Microglia (drug effects, metabolism, pathology)
• Peptide Fragments (pharmacology)
• Platelet Activating Factor (pharmacology)
• Postmortem Changes
• Signal Transduction (drug effects, physiology)
• Spectrometry, Fluorescence (methods)