Authors: Alice Weatherston
A research team from Ecole Polytechnique Fédérale de Lausanne (EPFL; Switzerland) has discovered an association between the production of lactate and the protection of neurons against excitotoxicity following trauma such as stroke or spinal cord injury. The findings were published in Scientific Reports recently.
Subsequent to acute trauma, neurons are subjected to excessive stimulation from NMDA receptors which interact with glutamate, resulting in a build-up of calcium ions and triggering toxic biochemical pathways that lead to cell damage or death. These receptors are a major medical research focus due to their links with a variety of neurological disorders such as epilepsy, schizophrenia, Parkinson’s and Alzheimer’s, as well as trauma events.
Researchers at EPFL and King Abdullah University of Science and Technology (Thuwal, Saudi Arabia), led by Pierre Magistretti (EPFL) therefore looked to investigate the effects of glutamate on cultured mouse neurons. They utilized the non-invasive imaging technique termed Digital Holographic Microscopy to visualize cell structure and dynamics at a nanometer-resolution. They also examined the role of lactate following previous indications that it may help to protect neurons against excitotoxicity.
The effects of glutamate, with and without lactate, were tested on the cultured mouse neurons. The results revealed that glutamate killed approximately 65% of neurons when there was no presence of lactate, however the additions of lactate reduced the loss of neurons to approximately 32%.
The team then determined the mechanism behind the neuroprotective properties of lactate by using a range of different receptor blockers on the mouse neurons. The analysis indicated that lactate is responsible for triggering the production of ATP and the consequential signalling cascade of defence mechanisms against the overactivation of the NMDA receptor.
The study’s findings help to advance our understanding of neuroprotection, which could provide further research pathways for the development of pharmacological approaches for reducing the damage caused by trauma.