April 29th, 2004
Boston Cure Project
A team of scientists studying the role of astrocytes in MS has suggested that the lack of a particular receptor in astrocytes may explain both the inflammatory and the neurodegenerative aspects of MS. In previous studies, these scientists discovered that a receptor normally expressed on the surface of astrocytes, the beta(2)-adrenoceptor, is absent on astrocytes in normal appearing white matter and plaque samples from MS subjects. (This receptor is, however, present to the same degree on cerebral cortex astrocytes in MS and control subjects.)
Beta(2)-adrenoceptors are bound by the neurotransmitter noradrenaline; this binding sets off subsequent events in the astrocyte that may be relevant to MS. First, noradrenaline binding inhibits the production of several inflammatory genes such as MHC class II molecules and tumor necrosis factor alpha. Without beta(2)-adrenoceptors, astrocytes can be induced to become reactive by the presence of inflammatory factors, and thus express molecules that help drive the inflammatory cascade. Second, noradrenaline binding also stimulates astrocytes to transform glycogen into lactate which neurons then take up and use as a source of energy. If this process is blocked, then neurons could become energy deprived and eventually misfunction and degenerate.
It is not known why astrocytes in white matter in MS are missing beta(2)-adrenoceptors. The authors speculate that a virus may be involved since canine distemper virus can have the same effect in animals.
One facet of MS that this theory does not appear to explain is the gray
matter atrophy found in MS, since gray matter astrocytes in MS subjects
do express beta(2)-adrenoceptors. However, the loss of these receptors
in astrocytes in white matter in MS is striking. The authors suggest testing
their hypothesis through clinical trials of compounds that act downstream
of the noradrenaline-beta(2)-adrenoceptor bond.
Copyright © 2004, Boston Cure Project