TY - ABST

T1 - Lactate receptor locations link neurotransmission, neurovascular coupling, and brain energy metabolism

AU - Bergersen, Linda Hildegard

AU - Lauritzen, Knut Husø

AU - Lauritzen, Fredrik

AU - Puchades, Maja

AU - Gjedde, Albert

PY - 2012

Y1 - 2012

N2 - BackgroundA major issue in neuroenergetics is the mechanism that links neurotransmission to brain energy metabolism. The modern understanding of the regulation of brain energy metabolism as it supports brain functional integrity suggests that a near-equilibrium feed-forward process establishes the necessary metabolic changes in advance of any changes of brain metabolite concentration. The outcome of such an adjustment is a homeostatically maintained environment where major metabolites such as ATP and ADP do not actually change under normal circumstances, because changing fluxes of metabolites are maintained by regulation of enzyme, transporter and receptor activities, rather than by changing concentrations of intermediaries. Hypothesis: Absent changes of ATP and ADP preclude a primary action of these molecules on the activity of mitochondria. Instead, new maps of the location of the lactate receptor GPR81 in brain suggest that depolarization of neuronal membranes acutely and directly affects the rate of aerobic glycolysis and hence the local generation of lactate, with consequences for the local concentration of cAMP and hence of second messenger cascades.MethodsWe used different novel antibodies against GPR81 and confocal immunofluorescence and electron microscopy.ResultsThe membrane locations of the GPR81 protein included the postsynaptic density of dendritic spines, and the endothelial part of the blood brain barrier in the mouse hippocampus.ConclusionsThis is the first identification of lactate receptors in cellular and subcellular structures of brain tissue. The location of receptors in endothelial membranes is consistent with a role of lactate in neurovascular coupling (Bergersen & Gjedde 2012; Gordon et al. 2008). The location of receptors in postsynaptic densities is consistent with a role in the regulation of brain energy metabolic mechanisms that also include the active movement of mitochondria to the necks of dendritic spines (Macaskill et al. 2009).

AB - BackgroundA major issue in neuroenergetics is the mechanism that links neurotransmission to brain energy metabolism. The modern understanding of the regulation of brain energy metabolism as it supports brain functional integrity suggests that a near-equilibrium feed-forward process establishes the necessary metabolic changes in advance of any changes of brain metabolite concentration. The outcome of such an adjustment is a homeostatically maintained environment where major metabolites such as ATP and ADP do not actually change under normal circumstances, because changing fluxes of metabolites are maintained by regulation of enzyme, transporter and receptor activities, rather than by changing concentrations of intermediaries. Hypothesis: Absent changes of ATP and ADP preclude a primary action of these molecules on the activity of mitochondria. Instead, new maps of the location of the lactate receptor GPR81 in brain suggest that depolarization of neuronal membranes acutely and directly affects the rate of aerobic glycolysis and hence the local generation of lactate, with consequences for the local concentration of cAMP and hence of second messenger cascades.MethodsWe used different novel antibodies against GPR81 and confocal immunofluorescence and electron microscopy.ResultsThe membrane locations of the GPR81 protein included the postsynaptic density of dendritic spines, and the endothelial part of the blood brain barrier in the mouse hippocampus.ConclusionsThis is the first identification of lactate receptors in cellular and subcellular structures of brain tissue. The location of receptors in endothelial membranes is consistent with a role of lactate in neurovascular coupling (Bergersen & Gjedde 2012; Gordon et al. 2008). The location of receptors in postsynaptic densities is consistent with a role in the regulation of brain energy metabolic mechanisms that also include the active movement of mitochondria to the necks of dendritic spines (Macaskill et al. 2009).

U2 - 10.1038/jcbfm.2012.80

DO - 10.1038/jcbfm.2012.80

M3 - Conference abstract in journal

VL - 32

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 1 suppl

M1 - P160

ER -