Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice
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| Názov: | Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice |
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| Autori: | Johannes M. van Noort, Sarah van de Berg, Erik Boddeke, Sandra Amor, Regina Peferoen-Baert, Marjolein Breur, David Baker, Paul van der Valk, Laura A. N. Peferoen, Gareth Pryce |
| Zdroj: | Peferoen, L A N, Breur, M, van de Berg, S, Peferoen-Baert, R, Boddeke, E H W G M, van der Valk, P, Pryce, G, van Noort, J M, Baker, D & Amor, S 2016, 'Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice', Immunology, vol. 149, no. 2, pp. 146-156. https://doi.org/10.1111/imm.12644 |
| Informácie o vydavateľovi: | Wiley, 2016. |
| Rok vydania: | 2016 |
| Predmety: | Male, Aging, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, T-Lymphocytes, experimental autoimmune encephalomyelitis, ALPHA-B-CRYSTALLIN, Apoptosis, Mice, Inbred Strains, neuroimmunology, multiple sclerosis, EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, MICROGLIA, Mice, 03 medical and health sciences, AGE, 0302 clinical medicine, Animals, Humans, BRAIN, Cells, Cultured, autoimmunity, CENTRAL-NERVOUS-SYSTEM, MULTIPLE-SCLEROSIS LESIONS, alpha-Crystallin B Chain, ACTIVATION STATUS, Up-Regulation, 3. Good health, Oligodendroglia, Oxidative Stress, THYMIC INVOLUTION, T-CELLS, Disease Progression, Female, Neurogenic Inflammation |
| Popis: | SummaryCurrent therapies for multiple sclerosis (MS) reduce the frequency of relapses by modulating adaptive immune responses but fail to limit the irreversible neurodegeneration driving progressive disability. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice recapitulates clinical features of MS including relapsing–remitting episodes and secondary‐progressive disability. To address the contribution of recurrent inflammatory events and ageing as factors that amplify progressive neurological disease, we examined EAE in 8‐ to 12‐week‐old and 12‐month‐old ABH mice. Compared with the relapsing–remitting (RREAE) and secondary progressive (SPEAE) EAE observed in young mice, old mice developed progressive disease from onset (PEAE) associated with pronounced axonal damage and increased numbers of CD3+ T cells and microglia/macrophages, but not B cells. Whereas the clinical neurological features of PEAE and SPEAE were comparable, the pathology was distinct. SPEAE was associated with significantly reduced perivascular infiltrates and T‐cell numbers in the central nervous system (CNS) compared with PEAE and the acute phase of RREAE. In contrast to perivascular infiltrates that declined during progression from RREAE into SPEAE, the numbers of microglia clusters remained constant. Similar to what is observed during MS, the microglia clusters emerging during EAE were associated with axonal damage and oligodendrocytes expressing heat‐shock protein B5, but not lymphocytes. Taken together, our data reveal that the course of EAE is dependent on the age of the mice. Younger mice show a relapsing–remitting phase followed by progressive disease, whereas old mice immediately show progression. This indicates that recurrent episodes of inflammation in the CNS, as well as age, contribute to progressive neurological disease. |
| Druh dokumentu: | Article |
| Jazyk: | English |
| ISSN: | 1365-2567 0019-2805 |
| DOI: | 10.1111/imm.12644 |
| Prístupová URL adresa: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/imm.12644 https://pubmed.ncbi.nlm.nih.gov/27388634 https://research.rug.nl/en/publications/f59b4b30-5520-4416-bc7f-c4b0a8283627 https://hdl.handle.net/11370/f59b4b30-5520-4416-bc7f-c4b0a8283627 https://doi.org/10.1111/imm.12644 https://core.ac.uk/display/148329278 https://www.rug.nl/research/portal/en/publications/ageing-and-recurrent-episodes-of-neuroinflammation-promote-progressive-experimental-autoimmune-encephalomyelitis-in-biozzi-abh-mice(f59b4b30-5520-4416-bc7f-c4b0a8283627).html https://onlinelibrary.wiley.com/doi/10.1111/imm.12644 https://research.vumc.nl/en/publications/ageing-and-recurrent-episodes-of-neuroinflammation-promote-progre http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011681 https://www.ncbi.nlm.nih.gov/pubmed/27388634 https://research.vumc.nl/en/publications/3cec7547-dc6c-4607-8c08-5a3f20c3ccac https://pure.amsterdamumc.nl/en/publications/33ccc01a-17a6-4bd7-a280-a9c5bde63dc3 https://doi.org/10.1111/imm.12644 |
| Rights: | Wiley Online Library User Agreement |
| Prístupové číslo: | edsair.doi.dedup.....ff0127d433a2bf1415ca55432d492c5a |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | SummaryCurrent therapies for multiple sclerosis (MS) reduce the frequency of relapses by modulating adaptive immune responses but fail to limit the irreversible neurodegeneration driving progressive disability. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice recapitulates clinical features of MS including relapsing–remitting episodes and secondary‐progressive disability. To address the contribution of recurrent inflammatory events and ageing as factors that amplify progressive neurological disease, we examined EAE in 8‐ to 12‐week‐old and 12‐month‐old ABH mice. Compared with the relapsing–remitting (RREAE) and secondary progressive (SPEAE) EAE observed in young mice, old mice developed progressive disease from onset (PEAE) associated with pronounced axonal damage and increased numbers of CD3+ T cells and microglia/macrophages, but not B cells. Whereas the clinical neurological features of PEAE and SPEAE were comparable, the pathology was distinct. SPEAE was associated with significantly reduced perivascular infiltrates and T‐cell numbers in the central nervous system (CNS) compared with PEAE and the acute phase of RREAE. In contrast to perivascular infiltrates that declined during progression from RREAE into SPEAE, the numbers of microglia clusters remained constant. Similar to what is observed during MS, the microglia clusters emerging during EAE were associated with axonal damage and oligodendrocytes expressing heat‐shock protein B5, but not lymphocytes. Taken together, our data reveal that the course of EAE is dependent on the age of the mice. Younger mice show a relapsing–remitting phase followed by progressive disease, whereas old mice immediately show progression. This indicates that recurrent episodes of inflammation in the CNS, as well as age, contribute to progressive neurological disease. |
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| ISSN: | 13652567 00192805 |
| DOI: | 10.1111/imm.12644 |