title: Inhibition of LINGO-1 promotes functional recovery after experimental spinal cord demyelination.
abstract: Blocking LINGO-1 has been shown to enhance remyelination in the rat lysolecithin-induced focal spinal cord demyelination model. We used transcranial magnetic motor-evoked potentials (tcMMEPs) to assess the effect of blocking LINGO-1 on recovery of axonal function in a mouse lysolecithin model at 1, 2 and 4weeks after injury. The role of LINGO-1 was assessed using LINGO-1 knockout (KO) mice and in wild-type mice after intraperitoneal administration of anti-LINGO-1 antagonist monoclonal antibody (mAb3B5). Response rates (at 2 and 4weeks) and amplitudes (at 4weeks) were significantly increased in LINGO-1 KO and mAb3B5-treated mice compared with matched controls. The latency of potentials at 4weeks was significantly shorter in mAb3B5-treated mice compared with controls. Lesion areas in LINGO-1 KO and mAb3B5-treated mice were reduced significantly compared with matched controls. The number of remyelinated axons within the lesions was increased and the G-ratios of the axons were decreased in both LINGO-1 KO and mAb3B5-treated mice compared with matched controls. These data provide morphometric and functional evidence of enhancement of remyelination associated with antagonism of LINGO-1.
authors: Department of Human Anatomy, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, China. Electronic address: zhangyongjie77@163.com.
authors: Yongjie
authors: Y
authors: Zhang
authors: Norton Neuroscience Institute, Norton Healthcare, 210 E. Gray Street, Suite 1102, Louisville, KY 40202, USA. Electronic address: yipingzhang50@gmail.com.
authors: Yi Ping
authors: YP
authors: Zhang
authors: Department of Discovery Biology, Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: blake.pepinsky@biogenidec.com.
authors: Blake
authors: B
authors: Pepinsky
authors: Department of Discovery Biology, Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: guanrong.huang@biogenidec.com.
authors: Guanrong
authors: G
authors: Huang
authors: Norton Neuroscience Institute, Norton Healthcare, 210 E. Gray Street, Suite 1102, Louisville, KY 40202, USA. Electronic address: LBES@earthlink.net.
authors: Lisa B E
authors: LB
authors: Shields
authors: Norton Neuroscience Institute, Norton Healthcare, 210 E. Gray Street, Suite 1102, Louisville, KY 40202, USA. Electronic address: cbshields1@gmail.com.
authors: Christopher B
authors: CB
authors: Shields
authors: Department of Discovery Biology, Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: sha.mi@biogenidec.com.
authors: Sha
authors: S
authors: Mi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D020127:Recovery of Function; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; C523678:LINGO1 protein, mouse; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
keywords: Demyelination; Electrophysiology; LINGO-1; Lysolecithin model; Morphometry; Multiple sclerosis; tcMMEP