Tyurikova, O; Zheng, K; Rings, A; Drews, A; Klenerman, D; Rusakov, DA; (2018) Monitoring Ca(2+) elevations in individual astrocytes upon local release of amyloid beta in acute brain slices. Brain Res Bull , 136 pp. 85-90. 10.1016/j.brainresbull.2016.12.007.

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Abstract

The pathogenesis of Alzheimer's disease (AD) is thought to involve acute neurotoxic effects exerted by oligomeric forms of amyloid-β 1-42 (Aβ). Application of Aβ oligomers in physiological concentrations have been shown to transiently elevate internal Ca(2+) in cultured astroglia. While the cellular machinery involved has been extensively explored, to what degree this important signalling cascade occurs in organised brain tissue has remained unclear. Here we adapted two-photon excitation microscopy and calibrated time-resolved imaging (FLIM), coupled with patch-clamp electrophysiology, to monitor Ca(2+) concentration ([Ca(2+)]) inside individual astrocytes and principal neurons in acute brain slices. Inside the slice tissue local micro-ejection of Aβ in sub-micromolar concentrations triggered prominent [Ca(2+)] elevations in an adjacent astrocyte translated as an approximately two-fold increase (averaged over ∼5min) in basal [Ca(2+)]. This elevation did not spread to neighbouring cells and appeared comparable in amplitude with commonly documented spontaneous [Ca(2+)] rises in astroglia. Principal nerve cells (pyramidal neurons) also showed Ca(2+) sensitivity, albeit to a lesser degree. These observations shed light on the extent and dynamics of the acute physiological effects of Aβ on brain cells in situ, in the context of AD.

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