Short-Term Cuprizone Feeding Induces Selective Amino Acid Deprivation with Concomitant Activation of an Integrated Stress Response in Oligodendrocytes
| Autor: | Moritz Daniel, Markus Kipp, Johannes Goldberg, Yasemin van Heuvel, Tim Clarner, Cordian Beyer, Marion Victor |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Biology Microgliosis Corpus Callosum Cuprizone Mice Cellular and Molecular Neuroscience Stress Physiological Internal medicine medicine Animals Integrated stress response Amino Acids chemistry.chemical_classification Alanine ATF3 Activating Transcription Factor 3 Myelin and Lymphocyte-Associated Proteolipid Proteins Feeding Behavior Cell Biology General Medicine Activating Transcription Factor 4 Oligodendrocyte Amino acid Mice Inbred C57BL Myelin-Associated Glycoprotein Oligodendroglia Endocrinology medicine.anatomical_structure Biochemistry chemistry Apoptosis Astrocytosis |
| Zdroj: | Cellular and Molecular Neurobiology. 33:1087-1098 |
| ISSN: | 1573-6830 0272-4340 |
| Popis: | Cuprizone [bis(cyclohexylidenehydrazide)]-induced toxic demyelination is an experimental approach frequently used to study de- and re-myelination in the central nervous system. In this model, mice are fed with the copper chelator cuprizone which leads to oligodendrocyte apoptosis and subsequent microgliosis, astrocytosis, and demyelination. The underlying mechanisms of cuprizone-induced oligodendrocyte death are still unknown. We analysed differences in amino acid levels after short-term cuprizone exposure (i.e., 4 days). Furthermore, an amino acid response (AAR) pathway activated in oligodendrocytes after cuprizone intoxication was evaluated. Short-term cuprizone exposure resulted in a selective decrease of alanine, glycine, and proline plasma levels, which was paralleled by an increase of apoptotic cells in the liver and a decrease of alanine aminotransferase in the serum. These parameters were paralleled by oligodendrocyte apoptosis and the induction of an AAR with increased expression of the transcription factors ATF-3 and ATF-4 (activating transcription factor-3 and -4). Immunohistochemistry revealed that ATF-3 is exclusively expressed by oligodendrocytes and localized to the nuclear compartment. Our results suggest that cuprizone-induced liver dysfunction results in amino acid starvation and in consequence to the activation of an AAR. We propose that this stress response modulates oligodendrocyte viability in the cuprizone animal model. |
| Databáze: | OpenAIRE |
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