Lactate, a waste product made in the brain and muscles after intense exercise, may protect neurons from damage following acute trauma such as stroke or spinal cord injury, according to a new mouse study by a Swiss and Saudi team of scientists.
When a person suffers from a stroke or spinal cord injury, the nerve cells experience excitotoxicity, or excessive stimulation. This extremely damaging process is also implicated in progressive neurodegenerative diseases, such as Alzheimer’s disease, the authors stated.
During excitotoxicity, NMDA receptors go into overdrive and overwhelm the target neuron with a barrage of electrical signals. NMDA receptors interact with the neurotransmitter glutamate and are a major target in research and medicine, as they are implicated in a number of disorders, including epilepsy, schizophrenia, Parkinson’s, and Alzheimer’s.
This barrage of electrical signals leads to a build-up of calcium ions inside the neuron, which triggers toxic biochemical pathways that can ultimately damage or kill it. Thus it is paramount that a person with stroke or spinal cord injury be treated as soon as possible to avoid excessive neuron death.
The researchers stated that while earlier research has suggested that lactate, a waste product of glucose metabolism, is able to protect neurons against excitotoxicity, exactly how this happens has remained a mystery until now.
In the new study, the team from the Ecole Polytechnique Fédérale de Lausanne (EPFL) and the King Abdullah University of Science and Technology investigated the effects of glutamate on cultured neurons taken from the brains of mice. They used a new, non-invasive imaging technique called digital holographic microscopy.
The scientists then tested the effects of glutamate on the mouse neurons with and without lactate. The results were significant: Glutamate killed 65 percent of the neurons, but with lactate, that number dropped to 32 percent.
The researchers then set out to determine exactly how lactate protects neurons. By using different receptor blockers on the mouse neurons, they determined that lactate triggers the production of ATP, the cell’s energy molecule.
In turn, ATP binds and activates another type of receptor in the neuron, which turns on a complex cascade of defense mechanisms. As a result, the neuron can withstand the barrage of signals from the NMDA receptor.
The findings significantly advance our understanding of neuroprotection, the authors stated, which can lead to improved pharmacological treatments to avoid the irreparable damage caused by stroke, spinal cord injury, and other trauma.
The study is published in the journal Scientific Reports.