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Central nervous system rather than immune cell-derived BDNF mediates axonal protective effects early in autoimmune demyelination
- Source :
- Acta Neuropathologica
- Publisher :
- Springer Nature
-
Abstract
- Brain-derived neurotrophic factor (BDNF) is involved in neuronal and glial development and survival. While neurons and astrocytes are its main cellular source in the central nervous system (CNS), bioactive BDNF is also expressed in immune cells and in lesions of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Previous data revealed that BDNF exerts neuroprotective effects in myelin oligodendrocyte glycoprotein-induced EAE. Using a conditional knock-out model with inducible deletion of BDNF, we here show that clinical symptoms and structural damage are increased when BDNF is absent during the initiation phase of clinical EAE. In contrast, deletion of BDNF later in the disease course of EAE did not result in significant changes, either in the disease course or in axonal integrity. Bone marrow chimeras revealed that the deletion of BDNF in the CNS alone, with no deletion of BDNF in the infiltrating immune cells, was sufficient for the observed effects. Finally, the therapeutic effect of glatiramer acetate, a well-characterized disease-modifying drug with the potential to modulate BDNF expression, was partially reversed in mice in which BDNF was deleted shortly before the onset of disease. In summary, our data argue for an early window of therapeutic opportunity where modulation of BDNF may exert neuroprotective effects in experimental autoimmune demyelination. peerReviewed
- Subjects :
- Central Nervous System
Male
Encephalomyelitis, Autoimmune, Experimental
Primary Cell Culture
Neuroimmunology
Clinical Neurology
Neurotrophins
BDNF
EAE
Conditional knock-out mice
Neuroprotection
Pathology and Forensic Medicine
03 medical and health sciences
Myelin
Mice
Cellular and Molecular Neuroscience
0302 clinical medicine
Neurotrophic factors
medicine
Animals
030304 developmental biology
Brain-derived neurotrophic factor
Mice, Knockout
0303 health sciences
Original Paper
biology
Brain-Derived Neurotrophic Factor
Experimental autoimmune encephalomyelitis
medicine.disease
Oligodendrocyte
Axons
3. Good health
Mice, Inbred C57BL
Disease Models, Animal
medicine.anatomical_structure
nervous system
Radiation Chimera
Immunology
Nerve Degeneration
biology.protein
Female
Neurology (clinical)
Medicine & Public Health
Neurosciences
Pathology
030217 neurology & neurosurgery
Neurotrophin
Subjects
Details
- Language :
- English
- ISSN :
- 00016322
- Volume :
- 123
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Acta Neuropathologica
- Accession number :
- edsair.doi.dedup.....3f212c35eb63e2bc49d3d6e45db54cd9
- Full Text :
- https://doi.org/10.1007/s00401-011-0890-3