| Abstract No.: | A-C1094 |
| Country: | Canada |
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| Title: | DISTURBED PROLIFERATIVE CAPACITY OF THE BRAIN DURING SYSTEMIC AUTOIMMUNE DISEASE |
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| Authors/Affiliations: | 1 Mile Stanojcic*; 1 Jane Foster; 1 Boris Sakic;
1 McMaster University, Hamilton, ON, Canada
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| Content: | Brain atrophy and neuronal degeneration of unknown etiology are frequent and severe concomitants of systemic lupus erythematosus (SLE). Objective: Using the murine MRL-lpr model, we presently examine reparative potential of the brain during chronic autoimmunity and inflammation. Materials and Methods: Mice received daily injections of bromodeoxyruridine (BrdU; 50μg/g) during the fifteenth week of age and after the last injection, ten from each strain were sacrificed in order to assess the survival and differentiation rates of newly generated brain cells. Neural atrophy was assessed using immunostaining of Fluoro Jade B, Ki67 and NeuN. Results: Severe autoimmune manifestations and brain atrophy were associated with a reduced diameter of BrdU+ cells in the subventricular zone suggesting disturbances in proliferation, increased number of Fluoro Jade B-positive cells in the subgranular zone of the dentate gyrus, and paradoxical increase of Ki67+/BrdU- cells in paraventricular nucleus. “Fusing” protuberances were observed in the lateral ventricles of autoimmune mice exclusively, suggesting discoordinated migration of neural stem cells. The choroid plexus in autoimmune MRL-lpr mice was consistently infiltrated with Ki67+/BrdU+ cells, suggesting proliferative leukocytosis in the main CSF-producing organ. Conclusion: The above results support the hypothesis that systemic autoimmune disease induces complex central nervous system pathology, which includes impaired regenerative capacity and cell demise in the main germinal centers. Moreover, proposed degeneration of the paraventricular nucleus may account for profound deficits in anxiety-related behavior and endocrine dysfunction during SLE-like disease.
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