Two-photon, live-imaging microscopy revealed a direct interaction between immune cells and neurons that plays a significant role in neuronal injury and may provide a therapeutic target for multiple sclerosis (MS), according to a study published online Sept. 23 in Immunity.
Multiple theories attempt to explain the role of the neuronal compartment in MS pathology. Neurobiologists focus on the loss of the protective myelin sheath, and immunologists stress the inflammatory milieu, explained Frauke Zipp, PhD, of Johannes Gutenberg University Mainz in Germany. Previous research has indicated that direct damage to neurons is prominent early in the disease, but “actual events leading to neural damages are not well-understood,” shared Zipp.
Zipp and colleagues sought to identify triggers of neurodegeneration by studying neuronal damage in mice with experimental autoimmune encephalomyelitis (EAE, an animal model of MS). The researchers observed direct synapse-like interactions between immune cells and neurons, with Th17 cells inducing toxic changes in neuronal calcium levels.
The results characterize neuronal dysfunction as early and potentially reversible, offering a potential therapeutic path to partially reverse damage. Specifically, fluctuations in neuronal intracellular calcium levels that were linked with cell injury were partially reversible when cells were exposed to compounds used to treat excitotoxicity.
“Immune-mediated reversible calcium increases in neurons are a viable target for future therapeutics,” offered Zipp.
The study also adds to the knowledge base and outlines the interaction between the immune system and nervous system, suggesting immune-mediated disturbances of the neurons contribute to MS.