title: Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis.
abstract: Brain-derived neurotrophic factor plays a key role in neuronal and axonal survival. Brain-derived neurotrophic factor is expressed in the immune cells in lesions of experimental autoimmune encephalomyelitis and multiple sclerosis, thus potentially mediating neuroprotective effects. We investigated the functional role of brain-derived neurotrophic factor in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Mice deficient for brain-derived neurotrophic factor in immune cells displayed an attenuated immune response in the acute phase of experimental autoimmune encephalomyelitis, but progressive disability with enhanced axonal loss in the chronic phase of the disease. In mice deficient for central nervous system-derived brain-derived neurotrophic factor via glial fibrillary acidic protein-crescentin-mediated deletion, a more severe course of experimental autoimmune encephalomyelitis and an overall increased axonal loss was observed. In a lentiviral approach, injection of brain-derived neurotrophic factor-overexpressing T cells led to a less severe course of experimental autoimmune encephalomyelitis and direct axonal protection. Our data imply a functional role of brain-derived neurotrophic factor in autoimmune demyelination by mediating axon protection.
authors.affiliation: Department of Neurology St. Josef Hospital, Ruhr-University Bochum, D-44791 Bochum, Germany. ralf.linker@rub.de
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.forename: De-Hyung
authors.initials: DH
authors.lastname: Lee
authors.forename: Seray
authors.initials: S
authors.lastname: Demir
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiese
authors.forename: Niels
authors.initials: N
authors.lastname: Kruse
authors.forename: Ines
authors.initials: I
authors.lastname: Siglienti
authors.forename: Ellen
authors.initials: E
authors.lastname: Gerhardt
authors.forename: Harald
authors.initials: H
authors.lastname: Neumann
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
authors.forename: Fred
authors.initials: F
authors.lastname: Lühder
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
mesh_terms: D000208:Acute Disease; D000818:Animals; D015551:Autoimmunity / Q000502:physiology*; D001369:Axons / Q000276:immunology / Q000473:pathology; D001921:Brain / Q000276:immunology / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D004185:Disability Evaluation; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009103:Multiple Sclerosis; D015213:Neuroimmunomodulation / Q000502:physiology; D020813:Receptor, trkB / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB