Acute sensitivity of astrocytes in the Substantia Nigra to oxygen and glucose deprivation (OGD) compared with hippocampal astrocytes in brain slices. (15th October 2018) - Karunasinghe, Rashika N.
Highlights: Astrocytic responses to oxygen and glucose deprivation (OGD) were investigated in brain slice, an in vitro ischemia model. OGD depolarized astrocytes in the Substantia Nigra and reduced GFAP immunoreactivity. The membrane potential of nigral astrocytes did not repolarize during reperfusion (10–15 min). In contrast, hippocampal astrocytes did not show acute ischemic sensitivity. The ischemic impairment of nigral astrocyte function may contribute to sudden-onset vascular forms of parkinsonism. Abstract: The Substantia Nigra is a brainstem nucleus critical for movement control. Although its dopamine-producing neurons degenerate in Parkinsons disease, little is known of the acute effects of ischemia in this region. We recently reported that oxygen and glucose deprivation (OGD) in brain slices, an in vitro ischemia model, evokes a profound depolarization and swelling of GABAergic neurons in the Substantia Nigra pars reticulata (SNr), but not dopaminergic neurons in the Substantia Nigra pars compacta (SNc). The current study characterised the effects of OGD on nigral astrocytes, and compared these with the established responses of astrocytes in the CA1 hippocampal region. Intracellular recordings were made from astrocytes at the border between SNc and SNr subregions, in midbrain slices from postnatal day 21–23 rats. Immunoreactivity for astrocyte-specific proteins was also assessed. OGD evoked a slow, then fast depolarization of nigral astrocytes. The fast phase developed during the anoxic depolarization (indicated by a fast negative shift of extracellular DC potential and increase in light transmittance) and rapid increase in extracellular K + concentration in the SNr. This biphasic response resembled the OGD-evoked depolarization of hippocampal astrocytes. However, unlike the partial repolarization seen in hippocampal cells after reperfusion with O2 and glucose, nigral astrocytes remained depolarized near 0 mV. In addition, immunoreactivity for glial fibrillary acidic protein-positive astrocytes markedly decreased in the Substantia Nigra after OGD, while in the hippocampus remained unchanged. These data indicate an acute post-ischemic withdrawal of astrocytic support in the Substantia Nigra, but not in the hippocampus.