New research describes how the inflammation characteristic of multiple sclerosis affects neurons
Inflammation destroys the junctions between neurons, slowing information transfer
With electrical signals zapping at speeds up to 288 km/h (180 mph), neurons are the most well-known cells in the central nervous system. They are the basic unit of information processing. Neurons transmit electrical signals to each other in neuronal circuits through junctions called synapses, and these junctions are formed between protrusions called spines.
The break down of synapses in large numbers can lead to cognitive decline. Multiple Sclerosis (MS) is one such debilitating disorder of the nervous system, which causes alternating phases of inflammation and recovery. The synapses of people with MS are destroyed progressively over time. But it is still unclear how and why this synapse loss occurs.
To better understand this process, a team of researchers at the Ludwig-Maximilians University in Germany injected inflammation-inducing factors into the brains of mice, to mimic MS as seen in humans. They looked at the brains of live mice across days using advanced light microscopy. Three days after the injection, during the inflammation phase, they saw widespread loss of a certain subset of synapses. As a result, neurons were not firing as actively as they should have been. However, once those synapses were re-established two weeks after injection, during the recovery phase, the neuronal activities of the mice were back to normal.
The researchers wanted to know why were only a certain subset of synapses lost, and how that occurred. To answer this, they tracked the spines on the neurons over time using calcium sensors. They found that spines with high levels of accumulated calcium were unstable. Then they identified a special immune cell, called a phagocyte, that sniffed out and ultimately removed the synapses on these unstable spines. When they blocked the activation of these phagocytes using inhibitor drugs, they saw that it prevented the loss of synapses.
This study helps uncover one of the mechanisms underlying the loss of synapses during MS, albeit in mice. And, importantly, they have identified a therapeutic target for drug development that may address the decline of cognitive abilities in people with MS and ultimately improve their quality of life.