Memory impairment and other cognitive changes are experienced by many people with MS, but the details of how this occurs are not clear. Now researchers supported in part by the National MS Society report evidence that a group of immune system proteins called “complement” may play a role in the loss of nerve connections (synapses) in the hippocampus, a part of the brain linked to memory. This study was published in Annals of Neurology by Drs. Iliana Michailidou, Valeria Ramaglia and colleagues in The Netherlands and Germany (Published online May 11, 2015).
Background: Memory problems occur at one time or another in more than half of people who have MS. Previous research has shown a link between cognitive problems and MS damage and tissue shrinkage in the hippocampus, a part of the brain involved in memory.
Some research has shown that microscopic connectors in the brain called “synapses” may be lost in some parts of the brain during the course of MS, but details have been lacking. Synapses are the point of communication between individual nerve cells, and they are critically important for all functions of the nervous system including memory. Synapses change for many different reasons, and many of these changes occur normally during development and normal aging. Synapses can be lost or gained as well as strengthened or weakened.
A group of proteins called “complement” plays a role in these normal changes in synapses. Complement proteins also assist the immune system in killing foreign invaders, such as bacteria. If normal mechanisms for controlling complement become altered, they may contribute to unwanted tissue damage.
The study: Drs. Ramaglia and team set out to determine the cause of synapse loss in the hippocampus in people with MS. The researchers examined samples of the hippocampus from brains donated by people who had primary-progressive MS or secondary-progressive MS in their lifetimes. They compared tissues that showed loss of myelin, the fatty substance that surrounds and protects nerve fibers and is destroyed in MS, and tissues that appeared normal, with intact myelin. They also compared MS samples to tissues from people without MS, and people with another neurological disease.
Results: Compared to brains from people without neurological disease, the investigators observed a decrease in the density of synapses in the hippocampus in tissues from people with MS with myelin loss as well as those with intact myelin. Two specific types of complement proteins (C1q and C3) were increased in MS tissue at the site of synapses, compared to the other tissue samples from people of the same age. MS brains were also positive for proteins that indicate biological stress (mitochondrial heat shock protein 70), but showed no signs of the type of complement implicated in some other diseases (C5b9).
Comment: These results suggest a role for specific components of complement activity in synaptic loss in the hippocampus in people with MS. In light of the important role the hippocampus plays in short and long-term memory, this study also suggests that complement activity may contribute to cognitive problems experienced by people with MS. If these results are confirmed and refined through additional research, it is possible that in the future, therapies that target the complement system may be useful for preventing or treating memory problems in people with MS.
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