How does lactate at the blood brain barrier alter neurological function?

Image: Wix AI

It has been shown that high intensity interval training (HIIT) can significantly increase the amount of lactate going to the brain. One approach to HITT is to consider four minutes of all out, high intensity exercise followed by four minutes of rest and to repeat that three more times, twice a week (4x4).

Lactate, traditionally viewed as merely a byproduct of anaerobic metabolism, has been increasingly recognized for its role in brain metabolism and neurological function. The brain can utilize lactate as an alternative energy source to glucose. Here’s how lactate at the blood-brain barrier (BBB) and within the brain can impact neurological function:

Energy Substrate:

• Neurons and glial cells, particularly astrocytes, can take up lactate. During periods of intense neuronal activity, lactate can be an important energy source for neurons. This is part of the astrocyte-neuron lactate shuttle hypothesis, where astrocytes metabolize glucose to lactate and then supply lactate to neurons.

Neurotransmitter Regulation:

• Lactate can modulate the release of neurotransmitters. For example, it's been suggested that lactate might influence the release of glutamate, the primary excitatory neurotransmitter in the brain, which plays a critical role in synaptic activity and plasticity.

Blood-Brain Barrier Transport:

• Lactate crosses the BBB through monocarboxylate transporters (MCTs). Changes in the expression or function of these transporters can alter the amount of lactate that enters the brain, impacting its availability as an energy source.

Neurovascular Coupling:

• Lactate has been implicated in neurovascular coupling, the process by which blood flow to the brain is increased in response to neuronal activity. Lactate might signal blood vessels to dilate, thus increasing the delivery of oxygen and glucose to meet the metabolic demands of active neurons.

Neuronal Recovery and Repair:

• After brain injury, lactate levels in the brain can increase, and there is evidence to suggest that lactate can support neuronal recovery and repair, possibly by serving as an energy substrate under conditions where glucose metabolism is compromised.

Memory and Learning:

• There is evidence that lactate can affect memory formation and consolidation. Lactate produced during exercise, for instance, may enhance plasticity-related processes that are important for learning and memory.

pH Regulation:

• Lactate can influence brain pH levels. While the brain has mechanisms to regulate pH, excessive lactate production and accumulation, as seen in conditions like hypoxia or ischemia, can lead to lactic acidosis and negatively affect brain function.

Signaling Molecule:

• Beyond being an energy substrate, lactate functions as a signaling molecule, potentially affecting gene expression and protein activity that can influence brain function and protection mechanisms.

Pathological Conditions:

• Elevated lactate levels can be a marker of certain pathological conditions such as mitochondrial disorders, and it's involved in the pathology of various neurological diseases. For example, in stroke, lactate accumulation due to anaerobic metabolism can contribute to neuronal injury.

The role of lactate in the brain is complex and context-dependent. It can be beneficial, providing energy and supporting various brain functions, but it can also be detrimental under certain pathological conditions. The ongoing research into lactate's multifaceted role in the brain continues to reshape our understanding of brain metabolism and offers potential therapeutic insights for neurological conditions.