Brain metabolic state dictates the polarity of astrocyte control over the cerebrovasculature

By G. Gordon, Hyun B Choi, G. Ellis‐Davies, B. MacVicar. Nature, 2008

726 citations recorded by the source corpus.

Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E2, leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/547aae5beecfe6e8b7d964141fcc4bc939ef4a77

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In Cellular and Molecular Neuroscience

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Citations in the corpus

Sugar for the brain: the role of glucose in physiological and pathological brain function (2013, background): “However, recent studies suggest that changes in the lactate:pyruvate ratio, and therefore the cytosolic NADH:NAD+ ratio [40] or increased lactate production [41, 42] may be at least partially responsible for vasodilation during neuronal activation.”
Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. (2011, background): “…oxide (NO), released from different cellular compartments (i.e., neurons, astrocytes, pericytes, and smooth muscle cells), have been implicated in the activity-dependent increase in CBF (Iadecola and Nedergaard, 2007; Gordon et al., 2008; Carmignoto and Gomez-Gonzalo, 2010; Attwell et al., 2010).”
Synaptic energy use and supply. (2012, positive): “Indeed, one way in which lactate may provide synapses with energy is by being employed as a prostaglandinmodulating messenger to increase blood flow (Gordon et al., 2008; Attwell et al., 2010).”
Sweet Sixteen for ANLS (2012, background): “If we add to this, the recent demonstrations that lactate metabolism has a critical role in neurovascular coupling (Gordon et al, 2008), as well as in recovery from hypoxia (Schurr et al, 1997) and in neuroprotection (Bliss et al, 2004; Berthet et al, 2009), it is clear that lactate utilization is…”
Astrocyte-neuron lactate transport is required for long-term memory formation (2011, positive): “Because lactate has been suggested to play an important role in cellular and organelle redox balance (Brooks, 2009), we may also hypothesize that lactate not only represents an energy source, but also mediates coordinated astrocyte-neuron cell-cell and intracellular responses important for cell sign”
Glial and neuronal control of brain blood flow (2010, neutral): “The build-up of arachidonic acid leads, in turn, to the production of its metabolites, including prostaglandins and epoxyeicosatrienoic acids (EETs), which dilate nearby arteriole”
Integrative regulation of human brain blood flow (2014, background): “neurovascular coupling, in response to local decreases in tissue oxygen (Pelligrino et al. 1995; Thompson et al. 2003; Iadecola & Nedergaard, 2007; Gordon et al. 2008; Leithner & Royl, 2014); (2) brain extracellular acidosis due to increased neuronal/glial anaerobic metabolism eliciting vascular dil”