Researchers Funded by National MS Society Pinpoint Direct Damage to Nerve Connections in Mice, Independent of Myelin Damage
• Researchers have found evidence that microscopic connectors in the brain called “synapses” are directly damaged during the course of MS-like disease in mice, in an area of the brain linked to cognitive function.
• The damage appeared to be unrelated to myelin damage, and was linked to a specific molecule called platelet-activating factor receptor.
• Further research will determine whether treatment that protects synapses in the hippocampus may preserve cognitive function in people with MS. The team is pursuing therapeutic candidates based on these findings.
• This research was funded in part by a National MS Society-American Brain Foundation (American Academy of Neurology) Clinician Scientist Development Award to Dr. Matthew Bellizzi.
• The team (Drs. Bellizzi, Harris Gelbard, and colleagues, from the University of Rochester Medical Center, in New York) has published results in The Journal of Neuroscience. (2016 Jan 27;36(4):1336-46.)
Background: MS involves immune attacks in the brain and spinal cord. During the course of MS, damage occurs to the myelin that surrounds and protects nerve fibers, and nerve cells and their axons are also damaged. Damage to nerve cells in MS has been linked to cognitive impairment, progressive disability and other symptoms.
The causes of nerve damage are not yet well understood, which has limited progress in developing therapies that prevent damage and preserve nerve function (neuroprotection) to slow or stop progressive disability. 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. A team at the University of Rochester has been attempting to determine the extent of damage to nerve cell fibers and synapses in brain, to find ways to protect nerves from damage.
The Study: The team, led by Matthew Bellizzi, MD, PhD, and Harris Gelbard, MD, PhD (University of Rochester), studied mice with the MS-like disease EAE. They measured the density of synapses in an area of the brain called the hippocampus. The hippocampus is involved in memory function. Although myelin was preserved, synaptic density was reduced by 28%, compared with mice that did not have EAE.
In another study, the team grew nerve cells from the hippocampus in laboratory dishes, and then added brain cells called microglia. This made the synapses more vulnerable to damage, and this damage seemed to be dependent on signals from a molecule called platelet-activating factor receptor (PAFR). To test this, the team administered an experimental molecule – BN52021 – that inhibits PAFR. Administering this molecule before EAE developed did not prevent the disease, but preserved synapses.
This research was funded in part by a National MS Society-American Brain Foundation (American Academy of Neurology) Clinician Scientist Development Award to Dr. Matthew Bellizzi. The team published results in The Journal of Neuroscience. (2016 Jan 27;36(4):1336-46.)
Next Steps: Further research will determine whether treatment that preserves synapses in the hippocampus can improve cognitive function in people with MS. According to a press release from the University of Rochester, the researchers are now focused on exploring potential therapeutic candidates based on these findings.
Read more about research to repair damaged tissue in MS
Read more about efforts to understand how MS affects cognitive function
Watch the educational video, Mood & Cognition in MS: [What you can do].