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

McLarnon, JG; Choi, HB; Lue, LF; Walker, DG; Kim, SU
Journal of neuroscience research, 81(3):426-435, 2005
Journal Title
Journal of neuroscience research
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.
MeSH terms
Adenosine Triphosphate/pharmacologyAlzheimer Disease/pathology*Amyloid beta-Peptides/pharmacologyAnalysis of VarianceCalcium/metabolism*Cells, CulturedDrug InteractionsFetusHumansMicroglia/drug effectsMicroglia/metabolism*Microglia/pathologyPeptide Fragments/pharmacologyPlatelet Activating Factor/pharmacologyPostmortem ChangesSignal Transduction/drug effectsSignal Transduction/physiology*Spectrometry, Fluorescence/methods
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Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
김, 승업
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