TY - JOUR
T1 - Multiple sclerosis
T2 - Death receptor expression and oligodendrocyte apoptosis in established lesions
AU - Cannella, Barbara
AU - Gaupp, Stefanie
AU - Omari, Kakuri M.
AU - Raine, Cedric S.
N1 - Funding Information:
Supported in part by USPHS grants NS 08952, NS 11920 and NS 07098; NMSS grant RG 1001-K-11; the MS Foundation; and the Wollowick Family Foundation.
PY - 2007/8
Y1 - 2007/8
N2 - To determine whether TNF and TRAIL death receptors (DR), and decoy receptors (DcR), play a role in oligodendrocyte depletion in the lesions of chronic multiple sclerosis (MS), we investigated the presence and functionality of these molecules on oligodendrocytes in MS and non-MS brain tissue and on human oligodendrocytes in vitro. For this, we performed immunocytochemistry, Western blotting, TUNEL and FACS analysis for the presence of DR and apoptosis in sections of fresh frozen CNS tissue from cases of chronic MS, other neurologic diseases and normals, and in fetal human oligodendrocytes in vitro. The results showed that although oligodendrocytes demonstrated both DR and DcR, particularly in vitro, there was no predilection of the phenomenon for MS and apoptosis of oligodendrocytes, common in cultures after ligation with TRAIL, was negligible in CNS tissue in situ. Thus, death of oligodendrocytes by apoptosis was an infrequent event in all human CNS samples examined. We postulate that while oligodendrocyte apoptosis might prevail during the initial stages of MS, from our findings other mechanisms probably account for their loss in the established lesion and decoy receptors may play a protective role in oligodendrocyte survival.
AB - To determine whether TNF and TRAIL death receptors (DR), and decoy receptors (DcR), play a role in oligodendrocyte depletion in the lesions of chronic multiple sclerosis (MS), we investigated the presence and functionality of these molecules on oligodendrocytes in MS and non-MS brain tissue and on human oligodendrocytes in vitro. For this, we performed immunocytochemistry, Western blotting, TUNEL and FACS analysis for the presence of DR and apoptosis in sections of fresh frozen CNS tissue from cases of chronic MS, other neurologic diseases and normals, and in fetal human oligodendrocytes in vitro. The results showed that although oligodendrocytes demonstrated both DR and DcR, particularly in vitro, there was no predilection of the phenomenon for MS and apoptosis of oligodendrocytes, common in cultures after ligation with TRAIL, was negligible in CNS tissue in situ. Thus, death of oligodendrocytes by apoptosis was an infrequent event in all human CNS samples examined. We postulate that while oligodendrocyte apoptosis might prevail during the initial stages of MS, from our findings other mechanisms probably account for their loss in the established lesion and decoy receptors may play a protective role in oligodendrocyte survival.
KW - Cell death
KW - Oligodendrocytes
KW - TRAIL
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UR - http://www.scopus.com/inward/citedby.url?scp=34447637949&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2007.05.018
DO - 10.1016/j.jneuroim.2007.05.018
M3 - Article
C2 - 17610960
AN - SCOPUS:34447637949
SN - 0165-5728
VL - 188
SP - 128
EP - 137
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
IS - 1-2
ER -
