Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor
- Author(s)
- Soilu-Hanninen, M; Epa, R; Shipham, K; Butzkueven, H; Bucci, T; Barrett, G; Bartlett, PF; Kilpatrick, TJ;
- Details
- Publication Year 2000-03-15,Volume 59,Issue #6,Page 712-721
- Journal Title
- JOURNAL OF NEUROSCIENCE RESEARCH
- Publication Type
- Journal Article
- Abstract
- Upregulated expression of the low-affinity neurotrophin receptor (p75) in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) has recently been demonstrated. To investigate whether p75 plays a role in disease pathogenesis, we adopted a gene therapy approach, utilizing antisense oligonucleotides to downregulate p75 expression during EAE. Phosphorothioate antisense oligonucleotides (AS), nonsense oligonucleotides (NS) or phosphate buffered saline (PBS) were injected daily for 18 days after immunization of SJL/J (H-2s)-mice with myelin proteolipid protein (PLP) peptide 139-151. In the AS group, there was a statistically significant reduction in both the mean maximal disease score (1.85 in the AS, 2.94 in the NS and 2.75 in the PBS-groups, respectively, P < 0.025) and in the cumulative disease incidence (approximate to 60% in the AS group and approximate to 90% in the control groups). Histological and immunohistochemical analysis showed reduced inflammation and demyelination, as well as reduced p75 expression at the blood-brain barrier (BBB) in the AS-treated mice in comparison with both control groups. There was no difference, however, in p75 expression on neural cells within the CNS between the three groups of mice. We conclude that p75 could play a proactive role in the pathogenesis of EAE and may exert its effect at the level of the BBB. J. Neurosci. Res. 59:712-721, 2000. (C) 2000 Wiley-Liss, Inc.
- Publisher
- WILEY-BLACKWELL
- Keywords
- NERVE GROWTH-FACTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NGF RECEPTOR; MULTIPLE-SCLEROSIS; TRK PROTOONCOGENE; CELL-DEATH; EXPRESSION; P75; SYSTEM; MICE
- Publisher's Version
- https://doi.org/10.1002/(SICI)1097-4547(20000315)59:6<712::AID-JNR3>3.0.CO;2-L
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-03-15 12:00:00