Functional Oxygen Sensitivity of Astrocytes

Abstract

In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short period of time. However, oxygen tension monitored by the peripheral (arterial) chemoreceptors is not sensitive to regional CNS differences in partial pressure of oxygen (P O 2 ) that reflect variable levels of neuronal activity or local tissue hypoxia, pointing to the necessity of a functional brain oxygen sensor. This experimental animal (rats and mice) study shows that astrocytes, the most numerous brain glial cells, are sensitive to physiological changes in P

Ganglionic GFAP+ glial Gq-GPCR signaling enhances heart functions in vivo

“…AAV8-DIO-GFAP-hM3Dq-mCherry (3 × 10 13 virus molecules/ml, 1.5 μl) was bilaterally injected into the medulla of Gfap-Cre mice. The medulla was located using stereotaxic coordinates: from the bregma -6.74 ± 0.1 mm caudal, 1.4 ± 0.1 mm lateral, and 5.7 mm ventral.…”

“…Although SNA is mainly considered a product of integration by neuronal networks, recent evidence suggests that Gq G protein-coupled receptor (Gq-GPCR) activation in glial fibrillary acidic protein-expressing (GFAP + ) glia (CNS astrocytes and non-myelinating peripheral glia) also contributes to homeostatic control of blood gases (11)(12)(13) and gastrointestinal motility (14,15) via modulation of local neuronal activity. Recently, we showed that selective activation of Gq-GPCR signaling in GFAP + glia in vivo led to acute changes in autonomic functions, including increases in heart rate and blood pressure (16).…”

Signal transduction in astrocytes: Localization and release of inorganic polyphosphate

“…Previously we found that even a short exposure of astrocytes to hypoxia results in an increase in intracellular calcium (Angelova et al, 2015). In the present study, a short episode of hypoxia induces the release of polyP by fusion of VNUT‐containing vesicles ( n  = 39, Figure 6f) suggesting that release of polyP from astrocytes may play a certain role in mediating the physiological response to brain hypoxia.…”

“…An Olympus total internal reflection fluorescence (TIRF) microscope was used to detect vesicular fusion events in astrocytes expressing VNUT–eGFP or CD63‐mKate, as described in detail previously (Angelova et al, 2015; Kasymov et al, 2013). Fluorescence was excited at 488 nm and collected at 500–530 nm for eGFP and excited at 488 nm and collected at 600–660 nm for mKate.…”

“…Purinoceptors are expressed by astrocytes, and readily respond to the increases in extracellular ATP concentration (Angelova et al, 2015; Coco et al, 2003; Gourine et al, 2010). Regulated exocytosis of signaling molecules by astrocytes may involve different types of secretory organelles (synaptic‐like microvesicles, dense‐core vesicles, lysosomes, exosomes, and ectosomes (Oya et al, 2013; Verkhratsky, Matteoli, Parpura, Mothet, & Zorec, 2016).…”