Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis.
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.
Linker
Ralf A
RA
Department of Neurology St. Josef Hospital, Ruhr-University Bochum, D-44791 Bochum, Germany. ralf.linker@rub.de
Lee
De-Hyung
DH
Demir
Seray
S
Wiese
Stefan
S
Kruse
Niels
N
Siglienti
Ines
I
Gerhardt
Ellen
E
Neumann
Harald
H
Sendtner
Michael
M
Lühder
Fred
F
Gold
Ralf
R
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
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB