Multiple sclerosis research: Myelin influences how brain cells send signals

ScienceDaily (July 22, 2011) — The development of a new cell-culture system that mimics how specific nerve cell fibers in the brain become coated with protective myelin opens up new avenues of research about multiple sclerosis. Initial findings suggest that myelin regulates a key protein involved in sending long-distance signals.

Multiple sclerosis (MS) is an autoimmune disease characterized by damage to the myelin sheath surrounding nerve fibers. The cause remains unknown, and it is a chronic illness affecting the central nervous system that has no cure.

MS has long been considered a disease of white matter, a reference to the white-colored bundles of myelin-coated axons that project from the main body of a brain cell. But researchers have discovered that the condition also affects myelinated axons scattered in gray matter that contains main bodies of brain cells, and specifically the hippocampus region, which is important for learning and memory.

Up to half of MS patients suffer cognitive deficits in addition to physical symptoms. Researchers suspect that cognitive problems are caused by abnormal electrical activities of the demyelinated axons extending from hippocampal cells, but until now have not been able to test myelin's role in this part of the brain.

Ohio State University researchers have created a system in which two types of cells interact in a dish as they do in nature: neurons from the hippocampus and other brain cells, called oligodendrocytes, whose role is to wrap myelin around the axons.

Now that the researchers can study how myelination is switched on and off for hippocampal neurons, they also can see how myelin does more than provide insulation -- it also has a role in controlling nerve impulses traveling between distant parts of the nervous system. Identifying this mechanism when myelin is present will help improve understanding of what happens when axons in this critical area of the brain lose myelin as a result of MS, researchers say.

So far, the scientists have used the system to show that myelin regulates the placement and activity of a key protein, called a Kv1.2 voltage-gated potassium channel, that is needed to maintain ideal conditions for the effective transmission of electrical signals along these hippocampal axons.

"This channel is important because it is what leads to electrical activity and how neurons communicate with each other downstream," said Chen Gu, assistant professor of neuroscience at Ohio State and lead author of the study. "If that process is disrupted by demyelination, disease symptoms may occur."

The study appears in the current (July 22, 2011) issue of the Journal of Biological Chemistry.

To create the cell culture system, the researchers began with hippocampus neurons from a rodent brain -- a cell type that Gu has worked with for years. In culture, these cells can grow and develop dendrites -- other branch-like projections off of neurons -- and axons as well as generate electrical activity and synaptic connections, the same events that occur in the brain.

The researchers then added oligodendrocytes, along with some of their precursor cells, to the same dish as the neurons. And eventually, after maturing, these oligodendrocytes began to wrap myelin around the axons of the hippocampal neurons.

This system takes about five weeks to create, but the trickiest part, Gu said, was developing the proper solution for this culture so that both kinds of cells would behave as nature intended.

"In the end, the composition of the culture medium is basically half from a solution that supports the neurons and half from a medium in which the oligodendrocytes function well. We know that all the cells were happy because we got myelin," said Gu, also an investigator in Ohio State's Center for Molecular Neurobiology.

With the system established, they then turned to experimentation to test the effects of the myelin's presence on these specific brain cells.

Nerve cells send their signals encoded in electrical impulses over long distances. Concerted actions of various ion channels are required for properly generating these nerve impulses. Potassium channels are involved at the late phase in an impulse, and its role is to return a nerve cell to a resting state after the impulse has passed through it and gear up for the next one. The Kv1.2 ion channel helps ensure that this process works smoothly.

By experimentally manipulating signal conditions with the new co-culture system, Gu and his colleague were able to establish part of the sequence of events required for myelinated hippocampal neurons to effectively get their signals to their targets. Starting with a protein known to be produced by myelin and axons, called TAG-1, a cell adhesion molecule, they traced a series of chemical reactions indicating that myelin on the hippocampal axons was controlling the placement and activity of the Kv1.2 ion channel.

"The analysis allowed us to see the signaling pathways involving myelin's regulation of the Kv1.2 channel's placement along the axon as well as fine-tuning of the channel's activity," Gu said.

When MS demyelinates these axons, the affected nerve cells don't get the message to rest, and subsequently can't prepare adequately to receive and transmit the next signal that comes along.

"This means a nerve impulse will have a hard time traveling through the demyelinated region," Gu said. "This shows that the ion channel is probably involved in the downstream disease progression of MS."

Gu envisions many additional uses for the new co-culture system, including additional studies of how myelin affects the behavior of other channels, proteins and molecules that function within axons, as well as to screen the effects of experimental drugs on these myelinated cells.

This work was supported by a Career Transition Fellowship Award from the National Multiple Sclerosis Society and a grant from the National Institute for Neurological Disorders and Stroke.

Gu conducted this study with Yuanzheng Gu, a research associate in the Department of Neuroscience at Ohio State.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Ohio State University. The original article was written by Emily Caldwell.

Journal Reference:

C. Gu, Y. Gu. Clustering and Activity Tuning of Kv1 Channels in Myelinated Hippocampal Axons. Journal of Biological Chemistry, 2011; 286 (29): 25835 DOI: 10.1074/jbc.M111.219113

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Group therapy helps multiple sclerosis patients cope with depression, study finds

ScienceDaily (June 13, 2011) — Offering Multiple Sclerosis sufferers emotional support through group therapy sessions could improve their quality of life and save the NHS almost £500 per patient, a study at The University of Nottingham has discovered.

Researchers are now planning a larger multi-centre study into the issue to establish whether psychological therapy should be incorporated into the MS services currently provided by the NHS.

The study, funded by the MS Society, was led by Professor Nadina Lincoln, of the University's Institute of Work, Health and Organisations. She said: "These are very encouraging findings as many people with MS have problems with depression and anxiety and there are few treatments provided in NHS clinical services to address these. It is important that the psychological effects of MS are fully recognised as they can have a devastating effect on people's lives."

Depression and anxiety are common among sufferers of MS, a disabling neurological condition that affects around 100,000 people in the UK.

Previous studies have suggested that depression in MS can lead to patients failing to take their medication and a reduced quality of life. National Institute for Health and Clinical Excellence (NICE) guidelines also recognise that many people with both MS and depression or anxiety would prefer not to take antidepressants and recommends that psychological therapies should be offered as an alternative.

For the Nottingham study researchers recruited MS patients currently attending clinics run by Nottingham University Hospitals NHS Trust, as well as inviting referrals from specialist MS nurses and placing adverts in publications produced by the MS Society.

The volunteers were asked to complete questionnaires about how MS affects their daily lives and the extent to which they felt in control.

The patients were then randomly divided into two groups of just over 70 people. One group received all the usual care offered to MS and were put on a waiting list to receive group therapy at the end of the study.

The other group were invited to attend a course of six two-hour sessions of group therapy attended by up to eight participants at a time. Each session was led by a research psychologist, supervised by a qualified clinical psychologist with experience of working with people with MS.

Each session focussed on a topic, such as worry, gloom and relationships and was followed by practical exercises in strategies to cope with emotional problems and group discussion. They finished with relaxation exercises and group members were given tasks centred on practising coping strategies between sessions.

To assess the effectiveness of the sessions, questionnaires were sent to the participants at both four and eight months later and the results of those who received treatment were compared to those on the waiting list only.

The researchers found that those MS sufferers who attended the group sessions had fewer problems with anxiety and depression, the impact of the disease on their daily lives was reduced and their quality of life improved.

In terms of potential savings to the NHS, the researchers have also collected information on cost, which will be submitted for a future publication. They found that costs were reduced by £470 per patient for those who attended the therapy sessions compared with usual care. It was shown to almost halve the cost of visits to the GP, falling from £11,340 at the start of the study to just £5,832 at the eight month follow up. The costs of outpatient hospital visits were also slashed from £32,592 at the beginning of the study to £21,534 at the eight-month follow-up.

The next stage of the research will be to assess whether the group therapy approach works equally well in other centres through a larger study with the hope that the treatment could potentially be provided through NHS services for those with MS.

Dr Susan Kohlhass from the MS Society said: "Knowing group-based sessions can reduce anxiety and depression is a strong development towards improving the quality of peoples' lives with MS. We are committed to funding work that will imminently benefit people with the condition and this is a great example. The next stage will be to find if this approach is as effective in other areas of the country."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Nottingham.

Journal Reference:

N. B. Lincoln, F. Yuill, J. Holmes, A. E. Drummond, C. S. Constantinescu, S. Armstrong, C. Phillips. Evaluation of an adjustment group for people with multiple sclerosis and low mood: a randomized controlled trial. Multiple Sclerosis Journal, 2011; DOI: 10.1177/1352458511408753

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here