Is lactate a volume transmitter of metabolic states of the brain?

Linda H Bergersen, Albert Gjedde, Linda H Bergersen, Albert Gjedde

Abstract

We present the perspective that lactate is a volume transmitter of cellular signals in brain that acutely and chronically regulate the energy metabolism of large neuronal ensembles. From this perspective, we interpret recent evidence to mean that lactate transmission serves the maintenance of network metabolism by two different mechanisms, one by regulating the formation of cAMP via the lactate receptor GPR81, the other by adjusting the NADH/NAD(+) redox ratios, both linked to the maintenance of brain energy turnover and possibly cerebral blood flow. The role of lactate as mediator of metabolic information rather than metabolic substrate answers a number of questions raised by the controversial oxidativeness of astrocytic metabolism and its contribution to neuronal function.

Keywords: central fatigue; lactate; lactate receptor; metabolic information; volume transmission.

Figures

FIGURE 1
FIGURE 1
In this illustration you can follow the two different mechanisms proposed: (a) Lactate regulates the formation of cAMP via the lactate receptor GPR81. (b) Lactate adjusts the NADH/NAD+ redox ratio. (c) Both the formation of cAMP and the adjustment of NADH/NAD+ redox ratio can be linked to the maintenance of brain energy turnover and neurovascular coupling. The role of lactate in neurovascular coupling is included in the figure, but not dealt with in the text, which focuses on cellular effects of lactate in brain tissue. The roles of lactate as mediator of metabolic information rather than metabolic substrate answer a number of questions raised by the aerobic glycolysis of astrocytes and its controversial contribution to neuronal function.

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