Astrocyte-mediated control of cerebral microcirculation. Trends Neurosci 26: 340-345

Department of Neurology, University of California-San Francisco, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Trends in Neurosciences (Impact Factor: 13.56). 08/2003; 26(7):340-4; author reply 344-5. DOI: 10.1016/S0166-2236(03)00141-3
Source: PubMed


Characterization of astrocyte Ca2+ dynamics has been a topic of considerable emphasis for more than a decade. Only recently, however, has the physiological significance of astrocyte Ca2+ signaling started to become clear. Several studies have shown that astrocyte Ca2+ levels become elevated in response to neuronal input and that this, in turn, influences synaptic activity. A novel function of astrocyte Ca2+ signaling has been described by Zonta et al., whereby neuron-induced astrocyte Ca2+ elevations can lead to secretion of vasodilatory substances from perivascular astrocyte endfeet, resulting in improved local blood flow. This finding represents a breakthrough in our knowledge both of astrocyte function and of the mechanism of activity-dependent cerebral blood flow regulation.

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    • "Astrocytes have pivotal roles in brain function, including the maintenance of osmotic balance and optimal ionic conditions for neurons (Kimelberg, 2005), K+ clearance from the extracellular space (Wallraff et al., 2006; Sibille et al., 2013), glucose and lactate metabolism (Allaman et al., 2011), neurotransmitter recycling of the two most abundant neurotransmitters in the brain, glutamate and GABA (Simard and Nedergaard, 2004), and immune responses (Dong and Benveniste, 2001; Farina et al., 2007). Moreover, astrocytes have end-feet that cover blood vessels and release vasoactive substances to regulate cerebral microcirculation (Anderson and Nedergaard, 2003; Zonta et al., 2003; Takano et al., 2006) and blood brain barrier (BBB) permeability (Alvarez et al., 2013). In fact, their end-feet physically constitute part of the BBB. "
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    ABSTRACT: The role of astrocytes in brain function has evolved over the last decade, from support cells to active participants in the neuronal synapse through the release of "gliotransmitters."Astrocytes express receptors for most neurotransmitters and respond to them through Ca(2+) intracellular oscillations and propagation of intercellular Ca(2+) waves. While such waves are able to propagate among neighboring astrocytes through gap junctions, thereby activating several astrocytes simultaneously, they can also trigger the release of gliotransmitters, including glutamate, d-serine, glycine, ATP, adenosine, or GABA. There are several mechanisms by which gliotransmitter release occurs, including functional hemichannels. These gliotransmitters can activate neighboring astrocytes and participate in the propagation of intercellular Ca(2+) waves, or activate pre- and post-synaptic receptors, including NMDA, AMPA, and purinergic receptors. In consequence, hemichannels could play a pivotal role in astrocyte-to-astrocyte communication and astrocyte-to-neuron cross-talk. Recent evidence suggests that astroglial hemichannels are involved in higher brain functions including memory and glucose sensing. The present review will focus on the role of hemichannels in astrocyte-to-astrocyte and astrocyte-to neuron communication and in brain physiology.
    Frontiers in Physiology 06/2014; 5:193. DOI:10.3389/fphys.2014.00193 · 3.53 Impact Factor
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    • "A crucial element that facilitates the integrating functions of astrocytes is the regulated exocytosis of chemical substances [9, 29, 42–44]. By this process, astrocytes exert modulatory influences on neighboring cells and are thought to participate in the control of synaptic circuits and cerebral blood flow [45] [46]. Exocytosis is an evolutionary trait of eukaryotic cells that leads in a given secretory cell to a release of chemical content by a fast mechanism into the extracellular space and thus to communication with neighboring cells. "
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    ABSTRACT: Astrocytes are highly secretory cells, participating in rapid brain communication by releasing glutamate. Recent evidences have suggested that this process is largely mediated by Ca(2+)-dependent regulated exocytosis of VGLUT-positive vesicles. Here by taking advantage of VGLUT1-pHluorin and TIRF illumination, we characterized mechanisms of glutamate exocytosis evoked by endogenous transmitters (glutamate and ATP), which are known to stimulate Ca(2+) elevations in astrocytes. At first we characterized the VGLUT1-pHluorin expressing vesicles and found that VGLUT1-positive vesicles were a specific population of small synaptic-like microvesicles containing glutamate but which do not express VGLUT2. Endogenous mediators evoked a burst of exocytosis through activation of G-protein coupled receptors. Subsequent glutamate exocytosis was reduced by about 80% upon pharmacological blockade of the prostaglandin-forming enzyme, cyclooxygenase. On the other hand, receptor stimulation was accompanied by extracellular release of prostaglandin E2 (PGE2). Interestingly, administration of exogenous PGE2 produced per se rapid, store-dependent burst exocytosis of glutamatergic vesicles in astrocytes. Finally, when PGE2-neutralizing antibody was added to cell medium, transmitter-evoked exocytosis was again significantly reduced (by about 50%). Overall these data indicate that cyclooxygenase products are responsible for a major component of glutamate exocytosis in astrocytes and that large part of such component is sustained by autocrine/paracrine action of PGE2.
    Neural Plasticity 01/2014; 2014(20):254574. DOI:10.1155/2014/254574 · 3.58 Impact Factor
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    • "Because arterioles and medium-sized vessels are surrounded by smooth muscle, it is possible that depression-related neurophysiological changes in vascular innervation bringabout microscopic vascular pathology. Arterioles respond to innervation from autonomic ganglia (Sandor, 1999; Hamel, 2006), to perivascular axons from subcortical centers (Hamel, 2006), and to the influence of factors linked to the activity of local neurons and glial cells (Anderson and Nedergaard, 2003; Attwell et al., 2010). In depression, there is evidence for abnormal local neuronal and glial metabolism and functional and neurochemical disturbances (Stockmeier et al., 1998; Hamel, 2006; Drevets et al., 2008; Ordway et al., 2011) in subcortical sources (locus coeruleus, raphe nuclei, and nucleus basalis) innervating arterioles. "
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    ABSTRACT: Objective: Late-life depression has been associated with risk for cerebrovascular pathology, as demonstrated in neuroimaging studies of older depressed patients, as well as mood disorder following cerebrovascular accidents. However, more research is needed on neuroanatomical changes in late-life depression, where there has been no clearly documented link to brain injury. Such studies should examine morphological changes in medium and small sized vessels that supply the cortical gray and white matter. Methods: The present study used a non-specific histological Nissl staining and a more vessel-specific immunolabeling with endothelial marker von Willebrand Factor (vWF) to estimate density and size of blood vessel segments in the orbitofrontal cortex of 16 older subjects with major depressive disorder (MDD) and 9 non-psychiatric comparison subjects. Results: The density of Nissl-stained vessel segments and of segments with perivascular spaces was higher in subjects with MDD than in comparison subjects in gray (GM) and white matter (WM). In GM, the density of vWF-immunoreactive segments with cross-sectional areas greater than 800 µm2 was higher in MDD. In WM, only the density of vWF-immunoreactive segments with patent perivascular spaces and diameters larger than 60 µm was higher in subjects with MDD. Also in the WM, only subjects with late-onset MDD presented a significantly higher density of vWF-positive segments than comparison subjects. Conclusions: In older subjects with MDD, there appear to be morphological changes that increase visibility of medium-sized vessel segments with some labeling techniques, and this increased visibility may be related to increased patency of perivascular spaces around arterioles.
    International Journal of Geriatric Psychiatry 09/2013; 28(9). DOI:10.1002/gps.3911 · 2.87 Impact Factor
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