Deficient p75 low-affinity neurotrophin receptor expression exacerbates experimental allergic encephalomyelitis in C57/BL6 mice

• Published in: Journal of neuroimmunology 2004-03, Vol.148 (1), p.41-53
• Main Authors: Copray, Sjef, Küst, Britta, Emmer, Bart, Young Lin, May, Liem, Robert, Amor, Sandra, de Vries, Helga, Floris, Sarah, Boddeke, Erik
• Format: Article
• Language: English
• Subjects: Animals; Blood Vessels - pathology; Blood Vessels - ultrastructure; CD11 Antigens - metabolism; CD3 Complex - metabolism; Central Nervous System - cytology; Central Nervous System - metabolism; Central Nervous System - pathology; Central Nervous System - ultrastructure; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Endothelial cell; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelial Cells - ultrastructure; Experimental allergic encephalomyelitis; Gene Expression - drug effects; Gene Expression - physiology; Glycoproteins; Immunization - methods; Immunohistochemistry - methods; Inflammation; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron - methods; Multiple Sclerosis; Myelin oligodendrocyte glycoprotein; Peptide Fragments; Probability; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor - genetics; Receptors, Nerve Growth Factor - metabolism; Time Factors
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2003.11.008

We have investigated the role of p75 NTR in inflammation in experimental allergic encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS). Induction of EAE in C57/BL6 wild-type mice resulted in expression of p75 NTR in endothelial cells in the CNS. In contrast to the clinical manifestation of EAE observed in wild-type C57/BL6 mice, mice deficient for p75 NTR (p75 NTR knockout mice) developed severe or lethal disease and concomitant increased levels of inflammation in the CNS. Our findings suggest a physiological significant role for p75 NTR in CNS endothelial cells during inflammation and involvement in preservation of blood–brain barrier integrity during a severe infiltrative attack.