Modulation of adult hippocampal neurogenesis during myelin-directed autoimmune neuroinflammation
| Autor: | Orhan Aktas, Petra Huehnchen, Timour Prozorovski, Andreas Kupsch, Anne Lesemann, Barbara Steiner, Philipp Klaissle, Susanne A. Wolf, Jens Ingwersen |
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| Rok vydání: | 2010 |
| Předmět: |
Doublecortin Protein
Encephalomyelitis Autoimmune Experimental Neurogenesis Fluorescent Antibody Technique Autoimmunity Cell Count Biology Hippocampus Myelin oligodendrocyte glycoprotein Cellular and Molecular Neuroscience Myelin Mice Random Allocation medicine Animals Neuroinflammation Myelin Sheath Gliogenesis Inflammation Neurons Reverse Transcriptase Polymerase Chain Reaction Dentate gyrus Experimental autoimmune encephalomyelitis medicine.disease Doublecortin medicine.anatomical_structure Neurology Immunology biology.protein Female Neuroscience |
| Zdroj: | Glia. 59(1) |
| ISSN: | 1098-1136 |
| Popis: | In chronic autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) clinical signs of cognitive dysfunction have been associated with structural changes in the hippocampus. Moreover, experimental studies indicate that inflammatory responses within the CNS modulate the homeostasis of newborn cells in the adult dentate gyrus (DG). However, it remained open whether such changes happen regardless of the primary immunological target or whether a CNS antigen-directed T lymphocyte-mediated autoimmune response may exert a specific impact. We therefore induced experimental autoimmune encephalomyelitis (EAE), a common model of MS serving as a paradigm for a CNS-specific immune response, by immunizing C57BL/6 mice with encephalitogenic myelin oligodendrocyte glycoprotein (MOG) p35-55. In EAE animals, we found enhanced de novo generation and survival of doublecortin (DCX)-positive immature neurons when compared with controls immunized with CNS-irrelevant antigen (ovalbumine). However, despite activation of neurogenesis, we observed a reduced capacity of these cells to generate mature neurons. Moreover, the high number of newly born cells retained the expression of the glial marker GFAP. These effects were associated with downregulation of pro-neurogenic factors Neurogenin1 and Neurogenin2 and dysregulation of Notch, β-catenin, Sonic Hedgehog (Shh) signaling as suggested by altered gene expression of effector molecules. Thus, a CNS antigen-specific immune response leads to an aberrant differentiation of neural precursors associated with dysbalance of signaling pathways relevant for adult hippocampal neurogenesis. These results may further extend our understanding of disturbed regeneration in the course of chronic inflammatory CNS diseases such as MS. |
| Databáze: | OpenAIRE |
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