Researchers from Germany have found that Multiple sclerosis (MS)-associated inflammation in the cerebral cortex destroys neural connections known as synapses that go on to impair neural activity. MS is a progressive chronic inflammatory disease in which patients' immune systems attack their central nervous system.
For the study, the researchers used various imaging techniques to study a mouse model of MS. In doing so, they found that MS-associated inflammation causes phagocytes, immune cells that clear out harmful cells like bacteria, to target and destroy dendritic spines, which are essential for nerve cell communication.
In particular, the researchers noted that the phagocytes targeted dendritic spines with abnormally high calcium levels, something that itself may be triggered by inflammation. Such changes in calcium levels are typical not just of late-stage MS, but also those in the early phases of neurodegeneration.
The loss of dendritic spines from inflammation, however, seems to be reversible in mouse models induced with an acute inflammatory reaction lasting just a few days. In these models, soon after inflammation was resolved, the researchers observed that numbers of dendritic spines and synapses were restored, and nerve cell activity returned to normal.
While these recovery mechanisms may not be possible for those with MS due to the chronic nature of the condition, the researchers say that therapeutics that work to inhibit phagocytes and their activity may help preserve nerve cell communication and slow down the progression of the disease.
Already having been shown to work in mouse models, the researchers note, however, that such an approach must not completely block phagocyte activity given their essential role in the overall immune response.
“Overall, our study identifies synapse loss as a key [disease-associated] feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy,” write the researchers.