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Small Aβ 1–42 oligomer‐induced membrane depolarization of neuronal and microglial cells: Role of N‐methyl‐D‐aspartate receptors
Author(s) -
Morkuniene Ramune,
Cizas Paulius,
Jankeviciute Silvija,
Petrolis Robertas,
Arandarcikaite Odeta,
Krisciukaitis Algimantas,
Borutaite Vilmante
Publication year - 2015
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.23510
Subject(s) - depolarization , nmda receptor , neurodegeneration , glutamate receptor , microglia , membrane potential , mitochondrial permeability transition pore , microbiology and biotechnology , chemistry , biology , biophysics , programmed cell death , receptor , biochemistry , apoptosis , medicine , immunology , inflammation , disease
Although it is well documented that soluble beta amyloid (Aβ) oligomers are critical factors in the pathogenesis of Alzheimer's disease (AD) by causing synaptic dysfunction and neuronal death, the primary mechanisms by which Aβ oligomers trigger neurodegeneration are not entirely understood. We sought to investigate whether toxic small Aβ 1–42 oligomers induce changes in plasma membrane potential of cultured neurons and glial cells in rat cerebellar granule cell cultures leading to neuronal death and whether these effects are sensitive to the N‐methyl‐D‐aspartate receptor (NMDA‐R) antagonist MK801. We found that small Aβ 1–42 oligomers induced rapid, protracted membrane depolarization of both neurons and microglia, whereas there was no change in membrane potential of astrocytes. MK801 did not modulate Aβ‐induced neuronal depolarization. In contrast, Aβ 1−42 oligomer‐induced decrease in plasma membrane potential of microglia was prevented by MK801. Small Aβ 1–42 oligomers significantly elevated extracellular glutamate and caused neuronal necrosis, and both were prevented by MK801. Also, small Aβ 1–42 oligomers decreased resistance of isolated brain mitochondria to calcium‐induced opening of mitochondrial permeability transition pore. In conclusion, the results suggest that the primary effect of toxic small Aβ oligomers on neurons is rapid, NMDA‐R‐independent plasma membrane depolarization, which leads to neuronal death. Aβ oligomers‐induced depolarization of microglial cells is NMDA‐R dependent. © 2014 Wiley Periodicals, Inc.