Centrally administered pertussis toxin inhibits microglia migration to the spinal cord and prevents dissemination of disease in an EAE mouse model.
BACKGROUND
Experimental autoimmune encephalomyelitis (EAE) models are important vehicles for studying the effect of infectious elements such as Pertussis toxin (PTx) on disease processes related to acute demyelinating encephalomyelitis (ADEM) or multiple sclerosis (MS). PTx has pleotropic effects on the immune system. This study was designed to investigate the effects of PTx administered intracerebroventricularly (icv) in preventing downstream immune cell infiltration and demyelination of the spinal cord.


RESULTS
EAE was induced in C57BL/6 mice with MOG(35-55). PTx icv at seven days post MOG immunization resulted in mitigation of clinical motor symptoms, minimal T cell infiltration, and the marked absence of axonal loss and demyelination of the spinal cord. Integrity of the blood brain barrier was compromised in the brain whereas spinal cord BBB integrity remained intact. PTx icv markedly increased microglia numbers in the brain preventing their migration to the spinal cord. An in vitro transwell study demonstrated that PTx inhibited migration of microglia.


CONCLUSIONS
Centrally administered PTx abrogated migration of microglia in EAE mice, limiting the inflammatory cytokine milieu to the brain and prevented dissemination of demyelination. The effects of PTx icv warrants further investigation and provides an attractive template for further study regarding the pleotropic effects of infectious elements such as PTx in the pathogenesis of autoimmune disorders.
Yin
Jun-xiang
JX
Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona, United States of America.
Tu
Jiang-long
JL
Lin
Hao-jie
HJ
Shi
Fu-dong
FD
Liu
Ru-lan
RL
Zhao
Chong-bo
CB
Coons
Stephen W
SW
Kuniyoshi
Sandra
S
Shi
Jiong
J
D000595:Amino Acid Sequence; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D003711:Demyelinating Diseases / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000473:pathology*; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D037342:Pertussis Toxin / Q000008:administration & dosage* / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D037342:Pertussis Toxin
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