Exercise has numerous benefits; it helps out the body’s cardiovascular system, brain, and digestive system. Now we may have another benefit to add to the list — protecting neurons from trauma damage.

Researchers led by EPFL have discovered how lactate, a waste product of glucose metabolism, can help keep neurons safe from damage following an acute trauma like a spinal cord injury or stroke, according to a study published in Scientific Reports. When one of these types of trauma occurs, a process called excitotoxicity is prompted. As the name might suggest, this phenomenon involves a toxic excitement of certain nerve cells, and is the reason the period immediately following a traumatic injury is so critical. The receptors implicated in excitotoxicity are NMDA receptors, which interact with the neurotransmitter glutamate.

Previous studies have suggested lactate, produced in muscles and the brain after intense exercise, could protect neurons against excitotoxicity. Exactly how this occurs, however, had remained a mystery until now.

The research team took on the problem by testing the effects of glutamate on neurons cultivated from the brains of mice using a new, non-invasive imaging technique called Digital Holographic Microscopy. The technique is capable of visualizing cell structure and dynamics with nanometer-level resolution. First, the scientists tested the effects of glutamate alone on the mouse neurons, and found that the neurotransmitter killed 65 percent of the neurons. When they added lactate to the equation, that number fell significantly — down to 32 percent.

With a goal of finding out how this happened, the team used different receptor blockers on the mouse neurons, and eventually determined that lactate triggers the productions of ATP. ATP is the cell’s energy molecule, which in turn binds to and activates a different receptor in the neuron, triggering a cascade of complex defense mechanisms. In the end, the neuron is able to withstand the barrage of signals from the NMDA receptor that would have otherwise killed it.

The breakthrough could lead to improved treatments and therapies after stroke, spinal cord injury, and other types of trauma by advancing our knowledge of neuroprotection. NMDA receptors, in addition to being involved in excitotoxicity, have been studied extensively in relation to epilepsy, schizophrenia, Parkinson’s and Alzheimer’s.

Source: Jourdain P, Allman I, rothenfusser K, Fiumelli H, Marquet P, Magistretti P, et al. L-lactate protects neurons against excitotoxicity: implication of an ATP mediated signaling cascade. Scientific Reports. 2016.