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Complement C3 mediates early hippocampal neurodegeneration and memory impairment in experimental multiple sclerosis

Bourel, Julien, Planche, Vincent, Dubourdieu, Nadège, Oliveira, Aymeric, Séré, Alexandra, Ducourneau, Eva-Gunnel, Tible, Marion, Maitre, Marlène, Lesté-Lasserre, Thierry, Nadjar, Agnes, Desmedt, Aline, Ciofi, Philippe, Oliet, Stéphane H., Panatier, Aude, Tourdias, Thomas·2021·Neurobiology of Disease
DOI 10.1016/j.nbd.2021.105533
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Image 2
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Fig. 2 Cellular origin of C3 in the dentate gyrus of EAE-mice.
Fig. 2 Cellular origin of C3 in the dentate gyrus of EAE-mice.CC-BY-NC-ND · From the PDF
Fig. 3 Pharmacological inhibition of C3 prevents neuromorphological alterations in the dentate gyrus of EAE-mice.
Fig. 3 Pharmacological inhibition of C3 prevents neuromorphological alterations in the dentate gyrus of EAE-mice.CC-BY-NC-ND · From the PDF
Fig. 4 Effect of C3KO on neuromorphological alterations in the dentate gyrus of EAE-mice.
Fig. 4 Effect of C3KO on neuromorphological alterations in the dentate gyrus of EAE-mice.CC-BY-NC-ND · From the PDF
Fig. 5 C3KO and pharmacological inhibition of C3 prevent microglial synapse engulfment in the dentate gyrus of EAE-mice. ( A ) Immunostaining of microglial cells (Iba1, red) with blue nuclear counterstain (DAPI), lysosomes (CD68, grey) and synapses (Homer, green) are shown as raw confocal images (top), as 3D isosurface reconstruction of microglial cells together with lysosomes located inside microglial cells (middle), and as homer puncta (bottom) inside lysosomes in two enlarged illustrative locations (right). Scale bar is 8 μ m ( B ) Quantification of Homer puncta in CD68 lysosomes per microglia. Number of microglia analyzed per group = 30-to-49 from N = 5 mice per group. Error bars indicate mean ± SEM. * p < 0.05 and ** p ≤ 0.01 for Kruskal-Wallis test and FDR correction. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 5 C3KO and pharmacological inhibition of C3 prevent microglial synapse engulfment in the dentate gyrus of EAE-mice. ( A ) Immunostaining of microglial cells (Iba1, red) with blue nuclear counterstain (DAPI), lysosomes (CD68, grey) and synapses (Homer, green) are shown as raw confocal images (top), as 3D isosurface reconstruction of microglial cells together with lysosomes located inside microglial cells (middle), and as homer puncta (bottom) inside lysosomes in two enlarged illustrative locations (right). Scale bar is 8 μ m ( B ) Quantification of Homer puncta in CD68 lysosomes per microglia. Number of microglia analyzed per group = 30-to-49 from N = 5 mice per group. Error bars indicate mean ± SEM. * p < 0.05 and ** p ≤ 0.01 for Kruskal-Wallis test and FDR correction. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)CC-BY-NC-ND · From the PDF
Fig. 6 Deletion of C3, either pharmacologically or by a transgenic approach, preserved memory abilities in EAE-mice. ( A ) Representation of the contextual fear conditioning paradigm in which the context is the only predictor of the footshock while the discrete tone is not (pseudorandom distribution of tone and footshock that are unpaired). ( B ) Comparison of EAE, control CFA and EAE treated with RMA ( N = 15 mice per group). Freezing rate is plotted over time when mice were re-exposed to the context or to the tone alone in a safe and familiar environment. From these evolutions, the freezing rate over the first 2 min of re-exposition to the context is plotted as well as the freezing ratio that quantifies the differential freezing to the tone compared to the pre- and posttone period. ( C ) Comparison of EAE, CFA and EAE induced in the C3KO background ( N = 13 to 18 mice per group). Error bars indicate mean ± SEM. * p < 0.05, ** p ≤ 0.01 for one-way ANOVA and Tukey post hoc .
Fig. 6 Deletion of C3, either pharmacologically or by a transgenic approach, preserved memory abilities in EAE-mice. ( A ) Representation of the contextual fear conditioning paradigm in which the context is the only predictor of the footshock while the discrete tone is not (pseudorandom distribution of tone and footshock that are unpaired). ( B ) Comparison of EAE, control CFA and EAE treated with RMA ( N = 15 mice per group). Freezing rate is plotted over time when mice were re-exposed to the context or to the tone alone in a safe and familiar environment. From these evolutions, the freezing rate over the first 2 min of re-exposition to the context is plotted as well as the freezing ratio that quantifies the differential freezing to the tone compared to the pre- and posttone period. ( C ) Comparison of EAE, CFA and EAE induced in the C3KO background ( N = 13 to 18 mice per group). Error bars indicate mean ± SEM. * p < 0.05, ** p ≤ 0.01 for one-way ANOVA and Tukey post hoc .CC-BY-NC-ND · From the PDF

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Research works printed but not linked: 53

  1. Acharjee, 2013, Altered cognitive-emotional behavior in early experimental autoimmune encephalitis--cytokine and hormonal correlates, Brain Behav. Immun., 33, 164, 10.1016/j.bbi.2013.07.003 · DOI
  2. Acharjee, 2018, Reduced microglial activity and enhanced glutamate transmission in the Basolateral amygdala in early CNS autoimmunity, J. Neurosci., 38, 9019, 10.1523/JNEUROSCI.0398-18.2018 · DOI
  3. Aguzzi, 2013, Microglia: scapegoat, saboteur, or something else?, Science, 339, 156, 10.1126/science.1227901 · DOI · Paper page
  4. Baxter, 2007, The origin and application of experimental autoimmune encephalomyelitis, Nat. Rev. Immunol., 7, 904, 10.1038/nri2190 · DOI
  5. Boos, 2004, Deletion of the complement anaphylatoxin C3a receptor attenuates, whereas ectopic expression of C3a in the brain exacerbates, experimental autoimmune encephalomyelitis, J. Immunol., 173, 4708, 10.4049/jimmunol.173.7.4708 · DOI
  6. Brink, 2005, The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions, J. Neuropathol. Exp. Neurol., 64, 147, 10.1093/jnen/64.2.147 · DOI · Paper page
  7. Calandreau, 2006, Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response, J. Neurosci., 26, 13556, 10.1523/JNEUROSCI.3713-06.2006 · DOI
  8. Chiaravalloti, 2008, Cognitive impairment in multiple sclerosis, Lancet Neurol., 7, 1139, 10.1016/S1474-4422(08)70259-X · DOI · Paper page
  9. Colasanti, 2016, Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis, Biol. Psychiatry, 80, 62, 10.1016/j.biopsych.2015.11.022 · DOI
  10. Compston, 2008, Multiple sclerosis, Lancet, 372, 1502, 10.1016/S0140-6736(08)61620-7 · DOI
  11. Desmedt, 2015, Adaptive emotional memory: the key hippocampal-amygdalar interaction, Stress, 18, 297, 10.3109/10253890.2015.1067676 · DOI
  12. Di Filippo, 2013, Effects of central and peripheral inflammation on hippocampal synaptic plasticity, Neurobiol. Dis., 52, 229, 10.1016/j.nbd.2012.12.009 · DOI
  13. Di Filippo, 2016, Persistent activation of microglia and NADPH oxidase [corrected] drive hippocampal dysfunction in experimental multiple sclerosis, Sci. Rep., 6, 20926, 10.1038/srep20926 · DOI
  14. Di Filippo, 2018, Multiple sclerosis and cognition: synaptic failure and network dysfunction, Nat. Rev. Neurosci., 19, 599, 10.1038/s41583-018-0053-9 · DOI · Paper page
  15. Dineen, 2009, Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis, Brain, 132, 239, 10.1093/brain/awn275 · DOI
  16. Dutta, 2011, Demyelination causes synaptic alterations in hippocampi from multiple sclerosis patients, Ann. Neurol., 69, 445, 10.1002/ana.22337 · DOI
  17. Feuillet, 2007, Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis, Mult. Scler., 13, 124, 10.1177/1352458506071196 · DOI
  18. Grabert, 2016, Microglial brain region-dependent diversity and selective regional sensitivities to aging, Nat. Neurosci., 19, 504, 10.1038/nn.4222 · DOI · Paper page
  19. Habtemariam, 2018, Molecular pharmacology of rosmarinic and salvianolic acids: potential seeds for Alzheimer’s and vascular dementia drugs, Int. J. Mol. Sci., 19, 10.3390/ijms19020458 · DOI
  20. Haji, 2012, TNF-alpha-mediated anxiety in a mouse model of multiple sclerosis, Exp. Neurol., 237, 296, 10.1016/j.expneurol.2012.07.010 · DOI
  21. Hammond, 2020, Complement-dependent synapse loss and microgliosis in a mouse model of multiple sclerosis, Brain Behav. Immun., 87, 739, 10.1016/j.bbi.2020.03.004 · DOI
  22. Ingram, 2014, Complement activation in multiple sclerosis plaques: an immunohistochemical analysis, Acta Neuropathol. Commun., 2, 53, 10.1186/2051-5960-2-53 · DOI
  23. Kaouane, 2012, Glucocorticoids can induce PTSD-like memory impairments in mice, Science, 335, 1510, 10.1126/science.1207615 · DOI
  24. Konsman, 2002, Cytokine-induced sickness behaviour: mechanisms and implications, Trends Neurosci., 25, 154, 10.1016/S0166-2236(00)02088-9 · DOI · Paper page
  25. Livak, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method, Methods, 25, 402, 10.1006/meth.2001.1262 · DOI · Paper page
  26. Ludwin, 2016, Astrocytes in multiple sclerosis, Mult. Scler., 22, 1114, 10.1177/1352458516643396 · DOI
  27. Mandolesi, 2015, Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis, Nat. Rev. Neurol., 11, 711, 10.1038/nrneurol.2015.222 · DOI
  28. Michailidou, 2015, Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus, Ann. Neurol., 77, 1007, 10.1002/ana.24398 · DOI
  29. Michailidou, 2017, Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease: implication for disease pathogenesis, Glia, 65, 264, 10.1002/glia.23090 · DOI
  30. Mishra, 2019, Parabrachial interleukin-6 reduces body weight and food intake and increases thermogenesis to regulate energy metabolism, Cell Rep., 26
  31. Morrow, 2010, Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline, Clin. Neuropsychol., 24, 1131, 10.1080/13854046.2010.511272 · DOI
  32. Nataf, 2000, Attenuation of experimental autoimmune demyelination in complement-deficient mice, J. Immunol., 165, 5867, 10.4049/jimmunol.165.10.5867 · DOI
  33. Pekna, 1998, Targeted disruption of the murine gene coding for the third complement component (C3), Scand. J. Immunol., 47, 25, 10.1046/j.1365-3083.1998.00274.x · DOI
  34. Planche, 2017, Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis, Brain Behav. Immun., 60, 240, 10.1016/j.bbi.2016.11.010 · DOI
  35. Planche, 2017, Pattern separation performance is decreased in patients with early multiple sclerosis, Brain Behav., 7, 10.1002/brb3.739 · DOI
  36. Planche, 2017, Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis, Mult. Scler., 23, 1214, 10.1177/1352458516675750 · DOI · Paper page
  37. Planche, 2018, Regional hippocampal vulnerability in early multiple sclerosis: dynamic pathological spreading from dentate gyrus to CA1, Hum. Brain Mapp., 39, 1814, 10.1002/hbm.23970 · DOI
  38. Ricklin, 2013, Complement in immune and inflammatory disorders: pathophysiological mechanisms, J. Immunol., 190, 3831, 10.4049/jimmunol.1203487 · DOI
  39. Rocca, 2018, The hippocampus in multiple sclerosis, Lancet Neurol., 17, 918, 10.1016/S1474-4422(18)30309-0 · DOI
  40. Sahu, 1999, Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b, Biochem. Pharmacol., 57, 1439, 10.1016/S0006-2952(99)00044-1 · DOI
  41. Sicotte, 2008, Regional hippocampal atrophy in multiple sclerosis, Brain, 131, 1134, 10.1093/brain/awn030 · DOI
  42. Sierra, 2014, Never-resting microglia: physiological roles in the healthy brain and pathological implications, Front. Cell. Neurosci., 8, 240, 10.3389/fncel.2014.00240 · DOI
  43. Small, 2014, Isolating pathogenic mechanisms embedded within the hippocampal circuit through regional vulnerability, Neuron, 84, 32, 10.1016/j.neuron.2014.08.030 · DOI
  44. Stephan, 2012, The complement system: an unexpected role in synaptic pruning during development and disease, Annu. Rev. Neurosci., 35, 369, 10.1146/annurev-neuro-061010-113810 · DOI · Paper page
  45. Stevens, 2007, The classical complement cascade mediates CNS synapse elimination, Cell, 131, 1164, 10.1016/j.cell.2007.10.036 · DOI · Paper page
  46. Szalai, 2007, Complement in experimental autoimmune encephalomyelitis revisited: C3 is required for development of maximal disease, Mol. Immunol., 44, 3132, 10.1016/j.molimm.2007.02.002 · DOI
  47. t Hart, 2011, EAE: imperfect but useful models of multiple sclerosis, Trends Mol. Med., 17, 119, 10.1016/j.molmed.2010.11.006 · DOI
  48. Veerhuis, 2011, Complement in the brain, Mol. Immunol., 48, 1592, 10.1016/j.molimm.2011.04.003 · DOI
  49. Watkins, 2016, Complement is activated in progressive multiple sclerosis cortical grey matter lesions, J. Neuroinflammation, 13, 161, 10.1186/s12974-016-0611-x · DOI
  50. Werneburg, 2020, Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease, Immunity, 52
  51. Wu, 2019, Complement C3 is activated in human AD brain and is required for neurodegeneration in mouse models of amyloidosis and Tauopathy, Cell Rep., 28
  52. Ziehn, 2010, Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune encephalomyelitis, EAE, Lab. Investig., 90, 774, 10.1038/labinvest.2010.6 · DOI
  53. Ziehn, 2012, Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease, J. Neurosci., 32, 12312, 10.1523/JNEUROSCI.2796-12.2012 · DOI

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Metadata

Authors
Bourel, J., Planche, V., Dubourdieu, N., Oliveira, A., Séré, A., Ducourneau, E.-G., Tible, M., Maitre, M., Lesté-Lasserre, T., Nadjar, A., Desmedt, A., Ciofi, P., Oliet, S. H., Panatier, A., & Tourdias, T.
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2021-12
Volume
160
Pages
105533
ISSN
0969-9961
DOI
10.1016/j.nbd.2021.105533
Cited by
58
References
16
Language
en
Licence
Funders
  • Centre National de la Recherche Scientifique
  • Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
  • Université de Bordeaux
  • Agence Nationale de la Recherche (ANR-10-LABX-43, ANR-10-LABX-57)
  • Institut National de la Santé et de la Recherche Médicale

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