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Gas6 Deficiency Increases Oligodendrocyte Loss and Microglial Activation in Response to Cuprizone-Induced Demyelination
- Publication Year :
- 2008
- Publisher :
- Society for Neuroscience, 2008.
-
Abstract
- The TAM family of receptor protein tyrosine kinases comprises three known members, namely Tyro3, Axl, and Mer. These receptors are widely expressed in the nervous system, including by oligodendrocytes, the cell type responsible for myelinating the CNS. We examined the potential role of the TAM family and of their principle cognate ligand, Gas6 (growth arrest gene 6), in modulating the phenotype of the cuprizone model of demyelination. We found that the expression profiles ofAxl,Mer, andGas6mRNA were increased in the corpus callosum in a temporal profile correlating with the increased migration and proliferation of microglia/macrophages in this model. In contrast, expression ofTyro3decreased, correlating with the loss of oligodendrocytes. Gas6 both promotedin vitrosurvival of oligodendrocytes (39.3 ± 3.1 vs 11.8 ± 2.4%) and modulated markers of activation in purified cultures of microglia (tumor necrosis factor α mRNA expression was reduced ∼48%). In Gas6−/−mice subjected to cuprizone-challenge, demyelination was greater than in control mice, within the rostral region of the corpus callosum, as assessed by luxol fast blue staining (myelination reduced by 36%) and by ultrastructural analysis. An increased loss of Gst-π (glutathioneS-transferase-π)-positive oligodendrocytes was also identified throughout the corpus callosum of Gas6−/−mice. Microglial marker expression (ionized calcium-binding adapter molecule 1) was increased in Gas6−/−mice but was restricted to the rostral corpus callosum. Therefore, TAM receptor activation and regulation can independently influence both oligodendrocyte survival and the microglial response after CNS damage.
- Subjects :
- Cell Survival
Central nervous system
Neurotoxins
Biology
C-Mer Tyrosine Kinase
Nerve Fibers, Myelinated
Luxol fast blue stain
Rats, Sprague-Dawley
Cuprizone
Mice
Proto-Oncogene Proteins
medicine
Animals
Gliosis
Receptor
Cells, Cultured
Chelating Agents
Mice, Knockout
Oncogene Proteins
Microglia
Cell Death
c-Mer Tyrosine Kinase
GAS6
General Neuroscience
Receptor Protein-Tyrosine Kinases
Articles
Molecular biology
Axl Receptor Tyrosine Kinase
Oligodendrocyte
Coculture Techniques
Rats
Mice, Inbred C57BL
Disease Models, Animal
Oligodendroglia
medicine.anatomical_structure
Immunology
Intercellular Signaling Peptides and Proteins
medicine.symptom
Demyelinating Diseases
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....341607194115bae33edefac100100c29