Lesional accumulation of RhoA(+) cells in brains of experimental autoimmune encephalomyelitis and multiple sclerosis.
OBJECTIVE
Infiltration of autoantigen-specific T cells and monocytes into the central nervous system is essential for the development of both experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). RhoA is one of the best-known members of Rho GTPases, and inhibition of RhoA has been shown to attenuate the progression of EAE. The aim of this study was to investigate the expression of RhoA in brains of EAE rats and MS tissue.


METHODS
EAE was induced by immunization with the synthetic peptide gpMBP68-84 in rats, and clinical severity was scored. RhoA expression pattern was investigated in brains of EAE rats at different time points and in different lesions of brain tissue specimens from six MS brains and five neuropathologically unaffected controls by immunohistochemistry.


METHODS
In EAE rat brains, accumulation of RhoA(+) cells reached maximal levels around Day 13, correlating to the clinical severity of EAE, and up-regulation lasted until the recovery stage of the disease. Double-labelling experiments showed that the major cellular sources of RhoA were reactive macrophages/microglia. While RhoA(+) cells in normal human brain parenchyma were rarely observed, RhoA expression was found to be spatially associated with MS lesions, showing a marked decrease from active lesions via chronic stages to its near absence in normal-appearing white matter. In addition, major RhoA(+) cells in brain parenchyma of MS were identified to be activated macrophages/microglia.


CONCLUSIONS
Our present data indicated that RhoA may play an important role during the effector phase of EAE and MS. Therefore, RhoA inhibitors might be a therapeutic option for MS patients.
Zhang
Z
Z
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany. zhangzhiren@yahoo.com
Schittenhelm
J
J
Meyermann
R
R
Schluesener
H J
HJ
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis*
D020742:rhoA GTP-Binding Protein