October 6, 2020 News by Patricia Inacio, PhD

Pathway and Its Proteins Found to Control Myelin Repair, Renewal

A pathway controlled by three proteins — Daam2, Nedd4, and VHL — was identified by researchers as a key regulator of myelin production during central nervous system development and regeneration after injury. Myelin, the protective fatty layer that covers nerve fibers and helps to speed transmission of signals between nerve cells,…

January 28, 2019 News by Jonathan Grinstein

Altered Oligodendrocyte Diversity Contributes to Multiple Sclerosis, Study Suggests

Subpopulations of oligodendrocytes — cells that produce the myelin sheath that protects nerve fibers — are altered in patients with multiple sclerosis, a study shows. These findings suggest that oligodendrocyte diversity and the different functions of these subpopulations might have a greater role in the disease than previously thought. The severity of MS varies greatly, and the patient's disability level does not correlate well with the degree of myelin loss. This suggests that other factors contribute to MS severity. One such factor may be that oligodendrocytes are heterogeneous — diverse in makeup and function. For example, oligodendrocytes in mouse spinal cords are known to naturally produce longer myelin sheaths than oligodendrocytes in the mouse brain. Additionally, individual oligodendrocytes have been shown to have different molecular makeups. However, the extent of human oligodendrocyte diversity and its possible contribution to MS pathology remains unknown. Researchers from the Karolinska Institutet and the MRC Centre for Regenerative Medicine studied the differences of individual human oligodendrocytes from healthy and MS brains to assess their diversity. Specifically, the team examined oligodendrocytes from the white matter areas of post-mortem human brains both from MS and non-MS patients. The team examined the RNA content — the messenger molecule carrying instructions from DNA for the production of proteins — from individual oligodendrocytes. Researchers identified groups of RNA molecules that defined features of oligodendrocytes from healthy human white matter. Some of these groups match those that defined oligodendrocytes in healthy mice. Strikingly, some of these RNA molecules in healthy brains were under-represented in oligodendrocytes from MS brains, whereas others were more prevalent. “We found that oligodendrocytes are a diverse population of cells and that different types are likely to have different functions in the brain,” Charles ffrench-Constant, the study's co-lead author, said in a Karolinska Institutet news release written by Katarina Sternudd. These differences in oligodendrocyte RNA content may indicate different functional states of oligodendrocytes in MS lesions. “The proportions of different resident oligodendrocytes in the lesions are changed, along with their properties, suggesting that they might have important roles in MS,” said Eneritz Agirre, PhD, a study co-author. Furthermore, the researchers believe that this altered diversity in oligodendrocytes in MS may be important to understand disease progression and develop therapeutic approaches. “Understanding which types of oligodendrocytes are most beneficial in repairing myelin will be crucial for maximizing the chances of developing much-needed treatments for MS,” said Anna Williams, PhD, study co-lead author. The team concluded that the changes in different oligodendrocyte subpopulations in MS suggest "a more complex role of these cells in the pathology of the disease, but also in regeneration of new cells,” said Gonçalo Castelo-Branco, PhD, another study co-lead author.

October 30, 2017 News by Patricia Silva, PhD

#MSParis2017 – Aerobic Exercise Seen to Quickly Strengthen Brain Connections in Patients

Aerobic exercise strengthens brain connections in people with relapsing-remitting multiple sclerosis, Jan-Patrick Stellmann, with University Medical Center Hamburg-Eppendorf in Germany, reported at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris that ran from Oct. 25–28. According to Stellmann, "aerobic exercises are considered to improve mobility, fatigue, depression and cognition in MS," and also to "promote neuroprotective or neuroregenerative mechanisms." For the study, the team used MRI to examine how exercise affected different types of brain connections. They recruited 57 RRMS patients and 30 healthy controls to the study. Women made up more than two-thirds of the patient group, which had a mean age of 39. Patients only had mild disability, with a mean score of 1.5 on the Expanded Disability Status Scale. Researchers randomly assigned about half the group to a supervised and individually adapted aerobic exercise program, consisting of 22 sessions of up to one hour each. Others were assigned to a waiting list — with the intent of taking up exercise after three months — and served as a control group. MRI scans at the study's beginning revealed that patients had more so-called functional connections, but fewer structural ones, than healthy controls. It is known from earlier studies that most RRMS patients show abnormalities in functional connections, but some researchers find increases while others decreases in these connections. Functional and structural connections appear on different types of MRI scans — ones that make use either of blood flow changes or of the properties of water molecules in the white matter of the brain. The deviations were particularly pronounced in highly connected hub regions, the researchers said. After three months, functional connections increased across the entire brain among exercising patients, but decreased in those on the waiting list. Structural connections also increased among patients who exercised, while no change was detected among control patients. Researchers also noted that exercising patients grew more local connections, mostly in hub regions, compared to those who did not exercise. While it is generally accepted that aerobic exercise promotes neuroprotective and regenerative processes within the brain, the study demonstrated that exercise, in only three months, did indeed affect how the brain is wired. "Short-term aerobic exercise increases functional and structural connectivity," Stellmann concluded. "Already after three months, exercise lead to functional and structural reorganization of brain networks." The researcher highlighted the difficulties in obtaining financial support for trials on exercise. And he emphasized that patients should be encouraged by their doctors to exercise regularly.

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