Transient Oxygen/Glucose Deprivation Causes a Delayed Loss of Mitochondria and Increases Spontaneous Calcium Signaling in Astrocytic Processes

Abstract

Recently, mitochondria have been localized to astrocytic processes where they shape Ca 2ϩ signaling; this relationship has not been examined in models of ischemia/reperfusion. We biolistically transfected astrocytes in rat hippocampal slice cultures to facilitate fluorescent confocal microscopy, and subjected these slices to transient oxygen/glucose deprivation (OGD) that causes delayed excitotoxic death of CA1 pyramidal neurons. This insult caused a delayed loss of mitochondria from astrocytic processes and increased colocalization of mitochondria with the autophagosome marker LC3B. The losses of neurons in area CA1 and mitochondria in astrocytic processes were blocked by ionotropic glutamate receptor ( (1) in the cytoplasm surrounding mitochondria (mitochondrially centered) and (2) traversing the space between mitochondria (extramitochondrial). The spatial spread, kinetics, and frequency of these events were different. The amplitude of both types was doubled and the spread of both types changed by ϳ2-fold 24 h after OGD. Together, these data suggest that pathologic activation of glutamate transport and increased astrocytic Ca 2ϩ through reversed Na ϩ /Ca 2ϩ exchange triggers mitochondrial loss and dramatic increases in Ca 2ϩ signaling in astrocytic processes.

Regulation of mitochondrial dynamics in astrocytes: Mechanisms, consequences, and unknowns

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Neutrophil-mediated and low density lipoprotein receptor-mediated dual-targeting nanoformulation enhances brain accumulation of scutellarin and exerts neuroprotective effects against ischemic stroke

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