Scientists Discover Key Myelin Sheath Component

    • Anonymous
      December 2, 2007 at 7:21 pm

      Vascular biologists make a significant discovery in neurobiology

      November 30, 2007 – Researchers investigating blood vessels at Barts and The London School of Medicine have hit upon a new discovery in neurobiology that could have implications for patients experiencing peripheral nerve disorders. Their work, which was conducted in close collaboration with scientists at Imperial College London, University College London, Cancer Research UK and the University of Geneva, features in this week’s edition (30 November 2007) of the renowned journal Science.

      Lead by Professor Sussan Nourshargh the research reports on the previously unknown expression and function of a particular cell adhesion molecule, junctional adhesion molecule-C (JAM-C), in peripheral nerves. JAM-C, largely associated to date with inflammatory disorders, was found to play a critical role in maintaining the integrity and function of peripheral nerves by forming an integral part of the insulating sheath that surrounds these nerves – the myelin.

      Together with their collaborators, Professor Nourshargh and team member Christoph Scheiermann, discovered that mice in which the JAM-C gene had been deleted showed neuronal functional defects – specifically, impaired nerve conduction and behavioural abnormalities indicating muscle weakness.

      The findings of the study also indicated that in nerves from patients with particular peripheral nerve disorders the expression of JAM-C was defective. Collectively this study describes a previously unrecognised role for JAM-C and identifies this molecule as a key player in regulating the structural integrity and function of peripheral nerves. The study also potentially provides insight into the causes of some peripheral nerve disorders and presents a strong platform for further research into this area.

      There are more than 100 kinds of peripheral nerve disorders affecting approximately 1 in 20 people, symptoms of which – often starting gradually and steadily worsening – include numbness, pain, tingling, muscle weakness and sensitivity to touch.

      Commenting on the significance of the research findings Professor Nourshargh said: “The discovery of JAM-C in peripheral nerves has made a major contribution to the field of neurobiology at a fundamental molecular level, but has also raised the possibility that defective expression and/or function of this molecule may be associated with the pathology of certain peripheral nerve disorders.”

      Queen Mary, University of London

    • Anonymous
      December 2, 2007 at 7:34 pm

      Boy these studies are interesting as they are important. I wonder where this will take us? A blood test to detect GBS or a flare up for CIDP before it is noticed by the patient to cut down on the degree of the relapse? Stem cells use that repairs quickly? A gene that is present for the people that suffer from any of these diseases? Interesting! :confused: This leaves me with many questions!

    • Anonymous
      December 3, 2007 at 11:13 am

      This is an interesting article. I came up with an idea how this molecule may play a role in autoimmune diseases like CIDP or GBS. It always has been a puzzle to me why our immune system does not get rid of autoimmune cells directed toward the myelin. Apparently it works correctly by getting rid of all other autoimmune cells or else we would be in really big trouble. What if our immune system no longer recognizes as “self” that part of the myelin which is lacking this new molecule. This would open it up for attack.

    • Anonymous
      December 6, 2007 at 3:16 pm


    • Anonymous
      December 10, 2007 at 2:08 am

      That’s interesting Norb. I’m thinking that with my other out of control immune functions like allergies that there is an immune system regulation issue. That although many autoimmune cells are not allowed to exist maybe the normal regulatory cells that are generated in our marrow have been modified to not put in check some specific t-cells.

      check this story out

      Blood stem cells fight invaders, study finds

      November 30, 2007 – No other stem cell is more thoroughly understood than the blood, or hematopoietic, stem cell. These occasional and rare cells, scattered sparingly throughout the marrow and capable of replenishing an entire blood system, have been the driving force behind successful bone marrow transplants for decades. Scientists, for the most part, have seen this as the hematopoietic stem cell’s (HSC) singular role: to remain in the bone marrow indefinitely and to replenish blood and immune system cells only when called upon.

      New research from the lab of Harvard Medical School professor of pathology Ulrich von Andrian, published in the November 30 edition of Cell, now suggests that HSCs’ biological role is far more versatile and dynamic. He and his colleagues have found that HSCs can travel from the bone marrow, through the blood system, and enter visceral organs where they perform reconnaissance missions in search of pathogenic invaders. Upon encountering an invader they immediately synthesize a defense, divide and mature, churning out new immune system cells such as dendritic cells and other leukocytes, right on the spot.

      “This process changes the way we look at blood stem cells,” says von Andrian.

      For almost five decades scientists have known that a fraction of HSCs will sometimes migrate from the bone marrow into the bloodstream. And while scientists have observed this phenomenon, they haven’t known exactly why the stem cells would do this, and what sort of itinerary they might follow once they entered the blood.

      A group in von Andrian’s lab, led by postdoctoral researcher and cardiologist Steffen Massberg, decided to explore this question.

      They began be extracting lymph samples from the thoracic duct of a mouse. The thoracic duct, a major component of the lymphatic system, routes the body’s excess fluids into the circulation, fluids that normally accumulate in organs. In that sense, it’s a kind of physiological storm drainage system. The group reasoned that any itinerary would eventually bring these cells into the lymph system, so it marked a logical starting point.

      After screening large samples of thoracic fluid, they discovered an extremely small population of cells that, after rigorous testing, behaved identically to blood stem cells. Further tests, which involved mice genetically engineered so that their blood stem cells could be detected through fluorescent microscopy, revealed that these cells were also scattered throughout visceral organs, such as liver, heart, and lung.

      “Taken all together, a picture developed suggesting that these cells migrated from the marrow and into the circulation where they would then leak out and enter the tissue,” says Massberg. “After that, the thoracic duct would empty them back into the circulation, where they could reenter the marrow. But the question was, why” What exactly are they doing””

      The group had found that the stem cells remain in the tissue for thirty-six hours before exiting into the thoracic duct. This suggested that they were conducting some kind of surveillance. To test this, Massberg and his colleagues injected a bacterial endotoxin into the mouse tissue. Within a matter of days, clusters of specialized immune cells formed in the infected areas.

      “Typical immune responses deplete local specialized immune cells,” says Massberg. “It appears that the hematopoietic stem cells initiate an immune response and replenish these specialized immune cells. It’s a way of sensing local environmental disturbances and responding locally.”

      But finally, the researchers identified the molecular mechanism that explained these observational data.

      After residing for a while in the organ tissue, the stem cells receive a lipid signal that enables them to exit into the thoracic duct. However, the presence of endotoxin disrupts the normal signaling cascade. When the receptors on the stem-cell surface that detect the pathogens become active, the cell’s ability to receive the lipid signal is blocked. The stem cells literally get stuck in the tissue, where they are then triggered to proliferate into immune cells.

      “That stem cells are actually a part of the immune system, rather than just giving rise to it, is a very provocative idea,” says von Andrian. “This opens up a number of new avenues for us to explore ways that our bodies fight pathogens.”

      The researchers are now looking at ways that other common diseases, like cancer, may exploit this process.

      Harvard Medical School[/quote]

      something instructs those hematopoietic stem cells to go about their business regulating immune function – some initial toxin contact or immune function causes some errant chemical instruction to go unchecked

    • Anonymous
      December 10, 2007 at 6:13 pm

      This is what I found worthy of sharing with you on this matter:

      [QUOTE][/Sticky molecule may hold key to nerve disorders
      Thu Nov 29, 2007 3:35pm EST

      By Ben Hirschler
      LONDON (Reuters) – A sticky molecule previously linked to inflammation also helps seal vital insulation around peripheral nerves, making it a potential target for new drugs against nerve disorders, scientists said on Thursday.
      The latest research suggests the molecule, known as JAM-C, could be a key player in regulating the way nerves work.
      In genetically modified mice without the adhesion molecule, the myelin insulation sheath protecting nerves deteriorates and the animals experience faulty nerve firing, muscle weakness and a shortened stride, researchers reported in the journal Science.
      The team also found that nerves of patients with certain peripheral nerve disorders had defective JAM-C.
      Taken together, the findings suggest the molecule is a key player in regulating the structure and function of peripheral nerves and its malfunction may cause a number of illnesses.
      JAM-C, which was discovered only recently, is already being studied as a target for new medicines involved in inflammation and as a possible route to fight cancer, since it seems to help tumors form new blood vessels.
      “This finding opens up yet another area that this molecule should be investigated in — but it’s very early days,” Sussan Nourshargh, professor of microvascular pharmacology at Barts and The London School of Medicine, said in an interview.
      Nourshargh made the discovery of the molecule’s role in peripheral nerves by accident, while investigating blood vessels. Her team then collaborated with scientists at Imperial College London, University College London, Cancer Research UK and the University of Geneva to advance the work further.
      There are more than 100 kinds of peripheral nerve disorders affecting approximately one in 20 people. They often afflict people with existing diseases like diabetes and lupus, a chronic autoimmune disease.
      Symptoms include numbness, pain, tingling, muscle weakness and sensitivity to touch. Problems often start gradually and steadily get worse.
      Nourshargh said the new molecule was not found in the central nervous system and was therefore unlikely to play a role multiple sclerosis.
      JAM-C seems to work by sealing off the insulation in the critical gaps between so-called Schwann cells, which produce the myelin layers that wrap around nerve cells.
      (Reporting by Ben Hirschler, editing by Paul Casciato)
      © Reuters2007All rights reserved

    • Anonymous
      December 10, 2007 at 6:39 pm

      Wow! This is very intresting. I hope that this will eventually lead to better treatments for cidp:)