Lactate Transport and Signaling in the Brain, Potential Therapeutic Targets and Roles in Body–Brain Interaction
Authors: Linda Hildegard Bergersen
DOI / Source: https://doi.org/10.1038/jcbfm.2014.206
Date: 26 November 2014
Reading level: Advanced
Why This Matters for Freedivers
Hard breath-holds (especially repeats) push CO₂ up and oxygen down, which changes how the brain uses fuel and how “brain chemistry” feels near the end of a dive. This paper explains why lactate isn’t just “burn” from muscles: it can feed the brain and also act like a signaling molecule, meaning intense apnea sessions could influence alertness, focus, and recovery in ways that aren’t captured by SpO₂ alone.
Synopsis
Most people still think of lactate as a waste product that causes fatigue. This review argues that lactate is better understood as a traffic-and-messaging molecule: it moves between cells as a fuel and it can act like a signal that changes how brain cells behave.
The first big idea is transport. Lactate (and similar molecules like pyruvate and ketone bodies) crosses membranes using “gatekeepers” called monocarboxylate transporters (MCTs). The brain uses several types: - MCT1 is emphasized at the blood–brain barrier, helping regulate lactate movement between blood and brain. - MCT4 is mostly linked to astrocytes (support cells) that are more glycolytic and tend to produce/export lactate. - MCT2 is strongly linked to neurons, especially around synapses, where energy demand spikes during activity.
This sets up a simple flow concept: lactate tends to move from where it is produced (often astrocytes and active tissue) to where it is used (often neurons and other oxidative cells). Importantly, when blood lactate rises (like during exercise), the direction can flip and lactate can move from blood into brain, where it can be used for energy and even for myelin-related processes.
The second big idea is signaling. The review highlights a lactate receptor called HCAR1 (also known as GPR81) found on brain cells and blood vessels. When lactate binds, it can influence intracellular signaling (notably cAMP), which means lactate can function like a “volume transmitter”—a signal that spreads beyond one synapse and changes the behavior of a wider area of tissue. The author discusses how this signaling could connect metabolism to brain activity, blood flow regulation, and plasticity-related pathways (including links with factors like BDNF).
The review also explores why this matters clinically: lactate availability can be protective after brain injury, and lactate transport/signaling might become a therapeutic target in conditions like cognitive decline, epilepsy, and neurodegeneration. The overall message is: lactate is not just a marker of “going anaerobic.” In the brain, it’s part fuel, part messenger, and part body–brain communication channel—especially relevant when the body is under metabolic stress.
Abstract
Lactate acts as a buffer between glycolysis and oxidative metabolism, moving between cells and tissues through monocarboxylate transporters (MCTs). In the brain, lactate may function both as an energy substrate and as a signaling molecule. After neuronal activation, glycolysis can outpace oxidation, producing lactate; at rest there is net lactate efflux from brain to blood, while elevated blood lactate (such as during exercise) can drive lactate influx into the brain, where it can support energy production and myelin-related processes. Lactate can also bind the receptor HCAR1 (GPR81) on brain cells and cerebral blood vessels and influence intracellular signaling (including cAMP). This review focuses on the localization and function of HCAR1 and the major brain MCTs (MCT1, MCT2, and MCT4), and discusses their potential as therapeutic targets and their possible role in mediating some beneficial brain effects associated with physical exercise.