Researchers at the Netherlands Institute for Neuroscience have discovered that the energy management of inhibitory brain cells is different compared to excitatory cells in our brain. Why is that the case and what is the link with multiple sclerosis?

Brain cells are connected to each other by axons, the parts of the neuron that transmit electrical signals. To do this efficiently, axons are wrapped in myelin, a lipid-rich material which increases the speed at which electrical pulses are conducted. The importance of myelin becomes apparent in diseases such as multiple sclerosis (MS), where myelin is broken down, which has detrimental effects on brain function. As a result of myelin loss, the conduction of electrical signals is disrupted, which also means that the energy costs of this process become much higher.

Myelin behaves differently depending on the cell type. Our brain consists of both excitatory and inhibitory brain cells. We need these inhibitors, known as interneurons, to structure the symphony of the many electrical pulses in our brain. When stimulating brain cells are randomly active with no brakes to direct this activity, communication between brain cells becomes less precise. Interneurons are therefore of great importance for efficient functioning of our brain.

The team around researcher Koen Kole and his supervisor Maarten Kole looked at a special type of interneuron: the Parvalbumin or PV cell. Although PV cells occupy only a small percentage of the cells in the cerebral cortex, they are very good at controlling surrounding networks of brain cells. This is mainly because of their extensive axons with many branches. They also have a high level of electrical activity. This costs a lot of energy, but it does ensure that PV cells can effectively inhibit surrounding cells. Remarkably, PV cells are wrapped with myelin only in the first few branches of their axon, leaving large parts of the axon uncovered. So what exactly does myelin do in these cells?

Myelin does appear to be important in PV cells. Previous studies on tissue from MS patients showed that PV cells die when myelin is lost. Apart from conduction, myelin also plays an important role in nourishing the cell. Nutrients from the myelin can be absorbed by mitochondria, the energy factories of the cell. Since PV cells use a lot of energy, it has been thought that myelin in these cells might play an important role in supporting the energy production of mitochondria.

Opposite effect from other cell types

The new study shows that this is indeed the case, in contrast to other cell types. In excitatory brain cells, mitochondria were evenly distributed along the axon, but in PV cells, the team found that axons with myelin contained more mitochondria. And when the myelin is reduced in an experimental setting, PV cells showed a decrease in the amount of mitochondria whereas in excitatory cells mitochondria become more abundant. And that’s new. In PV cells, mitochondria behave in an opposite way from what was previously known in the literature for other types of cells. But why exactly does this happen in these cells?

Researcher Koen Kole: ‘We suspect that it has to do with the fact that PV cells have an incredibly high energy demand due to their high level of activity. In addition, their axons are very thin compared to those of other cell types, which could further increase their energy consumption. PV cells may therefore be more dependent on external nutrients from the myelin. A next important step would be to better understand how myelin influences the energy usage in the axons of PV cells. Abnormalities in PV cells and mitochondria can be found in many other neurological disorders besides MS. It is therefore of high importance to gain more insight into the energy management in this cell type.’

Researchers from Rutgers Robert Wood Johnson Medical School’s Department of Neurology have traced a previously observed link between microscopic organisms in the digestive tract — collectively known as the gut microbiome — and multiple sclerosis (MS).

Their study in genetically altered miceand people supports the belief that dietary adjustments such as increased fiber may slow MS progression, and they are already working to test the effect of dietary interventions in MS patients.

“Unhealthy dietary habits such as low fiber and high fat consumption may have contributed to the steep rise of MS in the US,” said Kouichi Ito, an associate professor of neurology and senior author of the study published in Frontiers in Immunology. “In nations where people still eat more fiber, MS is far less common.”

MS is a degenerative condition in which the body’s immune system attacks the protective covering of nerves in the brain, spinal cord and eyes. According to the National Multiple Sclerosis Society, it affects nearly 1 million adults in the United States.

Several previous studies have differentiated the microbiomes of MS patients and healthy subjects, but, Ito said, they all noted different abnormalities, so it was impossible to tell what change, if any, was driving disease progression.

The Rutgers study, which was led by research associate Sudhir Kumar Yadav, used mice engineered with MS-associated genes to trace the link between alterations in the gut bacteria and an MS-like condition called experimental autoimmune encephalomyelitis (EAE).

As these mice matured — and simultaneously developed EAE and a gut inflammatory condition called colitis — the researchers observed increased recruitment of inflammatory cells (neutrophils) to the colon and production of an anti-microbial protein called lipocalin 2 (Lcn-2).

The study team then looked for evidence that the same process occurred in people with MS and found significantly elevated Lcn-2 levels in patient stool. This marker correlated with reduced bacterial diversity and increased levels of other markers of intestinal inflammation. Additionally, bacteria that seem to ease inflammatory bowel disease were reduced in MS patients with higher levels of fecal Lcn-2.

The study suggests that fecal Lcn-2 levels may be a sensitive marker for detecting unhealthy changes in the gut microbiome of MS patients. It also provides further evidence that high-fiber diets, which reduce gut inflammation, may help fight MS.

Rutgers is looking to test that hypothesis soon. Suhayl Dhib-Jalbut, a co-senior author of the paper who heads the medical school’s neurology department, is recruiting patients with MS for a trial that will determine how their microbiomes and immune systems are affected by a high-fiber supplement developed by Rutgers Microbiologist Liping Zhao.

Multiple Sclerosis (MS) is almost always accompanied by fatigue, a massive tiredness that is described by the vast majority of patients as the most distressing symptom. In a recent scientific study, a research group led by Stefan Seidel from the Department of Neurology at MedUni Vienna and AKH Vienna identified light therapy as a promising non-drug treatment option: patients included in the study showed a measurable improvement after just 14 days of use. The study results were recently published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.

For the first time, Stefan Seidel’s research team relied not only on surveys but also on objective measurements when selecting the test persons. For example, sleep-wake disorders were ruled out in the 26 participating MS patients, particularly with the assistance of various sleep medicine examinations. “In this manner, for example, we ensured that MS patients with fatigue do not suffer from sleep apnea or periodic leg movements during sleep. Both are sleep disorders that can lead to fatigue in everyday life,” elaborated study leader Stefan Seidel.

Performance improvement
The test persons – all patients of the Neurology Department at MedUni Vienna and AKH Vienna – were equipped with commercially available light sources for self-testing at home: Half of the participants received a daylight lamp with a brightness of 10,000 lux, while the other half received an identical lamp that emitted a red light with an intensity of <300 lux due to a filter. While the red light used by the control group showed no effect, the researchers were able to observe measurable successes in the other group after only 14 days: The participants who used their 10,000 lux daylight lamp for half an hour every day showed improved physical and mental performance after only a short period of time. In addition, the group of participants who had consumed bright light displayed less daytime sleepiness in comparison with the other group.

Up to 99 percent of patients
Fatigue is a severe form of tiredness and fatigability that occurs in 75 to 99 percent of people with MS and is described as particularly distressing. Nerve damage triggered by MS is being discussed as the cause. In addition to behavioural measures, such as regular rest breaks, various medications are currently available to alleviate fatigue, but some of these are associated with severe side effects. “The findings from our study represent a promising non-drug therapeutic approach,” Stefan Seidel affirms. However, the results still need to be confirmed in a subsequent larger-scale study. The exact background of the invigorating effect of light therapy on MS patients will also be the subject of further scientific research.

My MS fatigue increased recently and it was starting to impact my quality of life. I made some adjustments and it is getting better. Many autoimmune conditions can lead to chronic fatigue but there are diet and lifestyle changes we can implement to help with fatigue. Watch this video to see my top tips to manage fatigue.