Premium
Perturbations in calcium‐mediated signal transduction in microglia from Alzheimer's disease patients
Author(s) -
McLar James G.,
Choi Hyun B.,
Lue LihFen,
Walker Douglas G.,
Kim Seung U.
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20487
Subject(s) - microglia , endoplasmic reticulum , calcium , signal transduction , basal (medicine) , endocrinology , adenosine triphosphate , adenosine , biology , medicine , microbiology and biotechnology , chemistry , neuroscience , inflammation , insulin
Calcium‐sensitive fluorescence microscopy has been used to study Ca 2+ ‐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 Ca 2+ [Ca 2+ ]i, peak amplitudes (Δ[Ca 2+ ]i) and time courses of adenosine triphosphate (ATP) responses and amplitudes of an initial transient response and a subsequent second component of Ca 2+ influx through store‐operated channels (SOC) induced by platelet‐activating factor (PAF). Overall, AD microglia were characterized by significantly higher (20%) basal Ca 2+ [Ca 2+ ]i relative to ND cells. The Δ[Ca 2+ ]i of ATP and initial phase of PAF responses, which reflect rapid depletion of Ca 2+ 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 Ca 2+ 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 μM Aβ 1–42 applied for 24 hr). Overall, these data indicate significant abnormalities are present in Ca 2+ ‐mediated signal transduction in microglia isolated from AD patients. © 2005 Wiley‐Liss, Inc.