Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis

被引：161

作者：

Linker, Ralf A. ^{[1
]}

Lee, De-Hyung ^{[1
]}

Demir, Seray ^{[1
,2
,3
]}

Wiese, Stefan ^{[4
]}

Kruse, Niels ^{[2
,3
]}

Siglienti, Ines ^{[1
]}

Gerhardt, Ellen ^{[5
]}

Neumann, Harald ^{[6
,7
]}

Sendtner, Michael ^{[8
]}

Luehder, Fred ^{[2
,3
]}

Gold, Ralf ^{[1
]}

机构：

[1] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, D-44791 Bochum, Germany

[2] Univ Gottingen, Inst Multiple Sclerosis Res, D-37033 Gottingen, Germany

[3] Gemeinnutzige Hertie Stiftung, D-37033 Gottingen, Germany

[4] Ruhr Univ Bochum, Inst Mol Neurobiol, D-44801 Bochum, Germany

[5] Univ Gottingen, Dept Neurol, D-37033 Gottingen, Germany

[6] Univ Bonn, Inst Reconstruct Neurobiol, D-53127 Bonn, Germany

[7] Hertie Fdn, D-53127 Bonn, Germany

[8] Julius Maximilians Univ, Dept Clin Neurobiol, D-97080 Wurzburg, Germany

来源：

BRAIN | 2010年 / 133卷

关键词：

axonal damage; experimental autoimmune encephalomyelitis; neurotrophin; CENTRAL-NERVOUS-SYSTEM; T-CELLS; GLATIRAMER ACETATE; SPINAL-CORD; MESSENGER-RNA; TRANSGENIC MICE; AXON PATHOLOGY; ANIMAL-MODELS; GLIAL-CELLS; BDNF;

D O I：

10.1093/brain/awq179

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：2248 / 2263

页数：16

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