ApoE-deficient promotes blood-brain barrier disruption in experimental autoimmune encephalomyelitis via alteration of MMP-9.
Disruption of the blood-brain barrier (BBB) is a surrogate marker of acute inflammatory lesions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Data from experiments suggest that apolipoprotein E (ApoE) plays an important role in the antiinflammatory and immunological process in MS/EAE. Recent researches have shown that lack of ApoE leads to loss of cerebrovascular integrity and BBB breakdown causing neuronal injury. Cerebrovascular effects of ApoE might be another important element resulting to more susceptibility to MS/EAE. However, there is no direct evidence that ApoE dependently contributes to maintaining BBB integrity in EAE. In this study, we induced EAE in ApoE-/- mice and wild-type mice. During EAE, our results show that lack of ApoE increased the Evan's blue (EB) permeability of BBB. Furthermore, deficiency of ApoE upregulated MMP-9 expression activity but decreased the expression of endothelial cell tight junction integral proteins claudin-5 and occludin. Our result also suggests that the protective role of ApoE in EAE by maintaining BBB integrity could be another interesting therapeutic target at MS/EAE.
Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.
Minghua
M
Zheng
Junjie
J
Wei
Yulan
Y
Tang
Chengcheng
C
Yang
Yunfei
Y
Wei
Xiaoduan
X
Yin
Qianqian
Q
Liu
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000235:genetics / Q000378:metabolism
D001057:Apolipoproteins E; D062507:Claudin-5; D062793:Occludin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse