Multiple sclerosis oligodendrocytes

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Selmaj, K., Brosnan, C.F., Raine, C.S. (1991). Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65 oligodendrocytes in multiple sclerosis. Proc. Natl. Acad. Sci. USA 88, 6452-6456. 

Omari KM, John GR, Sealfon SC, et al. CXC chemokine receptors on human oligodendrocytes implications for multiple sclerosis. Brain 2005 128 1003-1015. 

Peterson JW, Bo L, Mork S, et al. VCAM-l-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions. J Neuropathol Exp Neurol 2002 61 539-546. 

Multiple sclerosis A disease characterised by the progressive demyelination of CNS neurons and the loss of oligodendrocytes. Cannabinoids may be of benefit in treating MS. 

Cannella, B. and Raine, C. S. Multiple sclerosis cytokine receptors on oligodendrocytes predict innate regulation. Ann. Neurol. 55 46-57, 2004. 

Some aspects of multiple sclerosis are reflected in the animal model experimental autoimmune encephalomyelitis, which is induced by immunization of susceptible animals with appropriate encephalogenic proteins or peptides. In these animals, if cultured adult stem cell neurospheres are injected into the bloodstream, injected cells can find their way to damaged portions of the nervous system and improve function in mice. How the injected cells augmented the recovery process is unclear. One possibility is that cells recruited to the lesions differentiated into oligodendrocytes and generated new myelin sheaths, but this seems unlikely in the face of ongoing cellular destruction. 

Iglesias, A., Bauer, J., Litzenburger, T. etal. T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36 220-234,2001. 

John, G. R., Shankar, S. L., Shafit-Zagardo, B. etal. Multiple sclerosis re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat. Med. 8 1115-1121,2002. 

Multiple sclerosis 58 64% myelin oligodendrocyte glycoprotein Infectious agents (Epstein-Barr virus), solvents, ultraviolet radiation/vitamin D, tobacco... 

Oligodendrocytes are present in the CNS as well and wrap around axons to form a myelin sheath. Myelin wraps into concentric layers that spiral around the axon. Gaps in the oligodendrocytes are the nodes of Ranvier, where the membrane maintains contact with extracellular fluid. The nodes serve to propagate the action potential in myelinated axons. Schwann cells perform an analogous function, myelinating axons in the peripheral nervous system. Not all neurons are myelinated, but myelination increases the metabolic efficiency of action potentials. Demyelination of neurons produces deficits in neuronal conduction, as is seen in multiple sclerosis. 

Multiple sclerosis (MS) is the most frequent inflammatory demyeli-nating disease of the central nervous system that affects worldwide about 2.5 million people with no cure. Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-induced EAE) in DA rats is an appropriate model for therapeutic testing, sharing many features with human multiple sclerosis. 

Bonetti B, Stegagno C, CanneUa B, Rizzuto N, Moreno G et al (1999) Activation of NF-kappaB and c-jun transcription factors in multiple sclerosis lesions. Implications for oligodendrocyte pathology. Am J Pathol 155 1433-1438... 

Wilson HC, Scolding NJ, Raine CS (2006) Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions. J Neuroimmunol 176 162-173... 

Coelho RP, Payne SG, Bittman R, Spiegel S, Sato-Bigbee C. The immunomodulator FTY720 has a direct cytoprotective effect in oligodendrocyte progenitors implications for the treatment of 193. multiple sclerosis. J. Pharmacol. Exp. Ther. 2007 323 626-635. 

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