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Phagocytic Roles of Glial Cells in Healthy and Diseased Brains

  • Jung, Yeon-Joo (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Chung, Won-Suk (Department of Biological Sciences, Korea Advanced Institute of Science and Technology)
  • Received : 2017.07.04
  • Accepted : 2017.09.26
  • Published : 2018.07.01

Abstract

Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as ${\beta}$-amyloid, huntingtin, and ${\alpha}$-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G. M., Cooper, N. R., Eikelenboom, P., Emmerling, M., Fiebich, B. L., Finch, C. E., Frautschy, S., Griffin, W. S., Hampel, H., Hull, M., Landreth, G., Lue, L., Mrak, R., Mackenzie, I. R., McGeer, P. L., O'Banion, M. K., Pachter, J., Pasinetti, G., Plata-Salaman, C., Rogers, J., Rydel, R., Shen, Y., Streit, W., Strohmeyer, R., Tooyoma, I., Van Muiswinkel, F. L., Veerhuis, R., Walker, D., Webster, S., Wegrzyniak, B., Wenk, G. and Wyss-Coray, T. (2000) Inflammation and Alzheimer's disease. Neurobiol. Aging 21, 383-421. https://doi.org/10.1016/S0197-4580(00)00124-X
  2. Allen, N. J. and Barres, B. A. (2005) Signaling between glia and neurons: focus on synaptic plasticity. Curr. Opin. Neurobiol. 15, 542-548. https://doi.org/10.1016/j.conb.2005.08.006
  3. Allen, N. J., Bennett, M. L., Foo, L. C., Wang, G. X., Chakraborty, C., Smith, S. J. and Barres, B. A. (2012) Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature 486, 410-414. https://doi.org/10.1038/nature11059
  4. Araque, A., Sanzgiri, R. P., Parpura, V. and Haydon, P. G. (1999) Astrocyte-induced modulation of synaptic transmission. Can. J. Physiol. Pharmacol. 77, 699-706. https://doi.org/10.1139/y99-076
  5. Austin, S. A., Floden, A. M., Murphy, E. J. and Combs, C. K. (2006) ${\alpha}$-synuclein expression modulates microglial activation phenotype. J. Neurosci. 26, 10558-10563. https://doi.org/10.1523/JNEUROSCI.1799-06.2006
  6. Bellesi, M., de Vivo, L., Chini, M., Gilli, F., Tononi, G. and Cirelli, C. (2017) Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex. J. Neurosci. 37, 5263-5273. https://doi.org/10.1523/JNEUROSCI.3981-16.2017
  7. Benkler, C., Ben-Zur, T., Barhum, Y. and Offen, D. (2013) Altered astrocytic response to activation in SOD1(G93A) mice and its implications on amyotrophic lateral sclerosis pathogenesis. Glia 61, 312-326. https://doi.org/10.1002/glia.22428
  8. Bolmont, T., Haiss, F., Eicke, D., Radde, R., Mathis, C. A., Klunk, W. E., Kohsaka, S., Jucker, M. and Calhoun, M. E. (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J Neurosci. 28, 4283-4292. https://doi.org/10.1523/JNEUROSCI.4814-07.2008
  9. Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., Thompson, W. J. and Barres, B. A. (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264-278. https://doi.org/10.1523/JNEUROSCI.4178-07.2008
  10. Chen, K., Iribarren, P., Hu, J., Chen, J., Gong, W., Cho, E. H., Lockett, S., Dunlop, N. M. and Wang, J. M. (2006) Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid ${\beta}$ peptide. J. Biol. Chem. 281, 3651-3659. https://doi.org/10.1074/jbc.M508125200
  11. Cho, K. J., Cheon, S. Y. and Kim, G. W. (2016) Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q. Sci. Rep. 6, 18840. https://doi.org/10.1038/srep18840
  12. Chung, W. S. and Barres, B. A. (2012) The role of glial cells in synapse elimination. Curr. Opin. Neurobiol. 22, 438-445. https://doi.org/10.1016/j.conb.2011.10.003
  13. Chung, W. S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., Smith, S. J. and Barres, B. A. (2013) Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504, 394-400. https://doi.org/10.1038/nature12776
  14. Chung, W. S., Verghese, P. B., Chakraborty, C., Joung, J., Hyman, B. T., Ulrich, J. D., Holtzman, D. M. and Barres, B. A. (2016) Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes. Proc. Natl. Acad. Sci. U.S.A. 113, 10186-10191. https://doi.org/10.1073/pnas.1609896113
  15. Clarke, L. E. and Barres, B. A. (2013) Emerging roles of astrocytes in neural circuit development. Nat. Rev. Neurosci. 14, 311-321. https://doi.org/10.1038/nrn3484
  16. Clement, A. M., Nguyen, M. D., Roberts, E. A., Garcia, M. L., Boillee, S., Rule, M., McMahon, A. P., Doucette, W., Siwek, D., Ferrante, R. J., Brown, R. H., Jr., Julien, J. P., Goldstein, L. S. and Cleveland, D. W. (2003) Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 302, 113-117. https://doi.org/10.1126/science.1086071
  17. Cuyvers, E., Bettens, K., Philtjens, S., Van Langenhove, T., Gijselinck, I., van der Zee, J., Engelborghs, S., Vandenbulcke, M., Van Dongen, J., Geerts, N., Maes, G., Mattheijssens, M., Peeters, K., Cras, P., Vandenberghe, R., De Deyn, P. P., Van Broeckhoven, C., Cruts, M. and Sleegers, K. (2014) Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia. Neurobiol. Aging 35, 726.e11-726.e19. https://doi.org/10.1016/j.neurobiolaging.2013.09.009
  18. Depboylu, C., Schafer, M. K., Arias-Carrion, O., Oertel, W. H., Weihe, E. and Hoglinger, G. U. (2011) Possible involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson disease. J. Neuropathol. Exp. Neurol. 70, 125-132. https://doi.org/10.1097/NEN.0b013e31820805b9
  19. Diniz, L. P., Matias, I. C., Garcia, M. N. and Gomes, F. C. (2014) Astrocytic control of neural circuit formation: highlights on TGF-${\beta}$ signaling. Neurochem. Int. 78, 18-27. https://doi.org/10.1016/j.neuint.2014.07.008
  20. Dong, J. H., Ying, G. X. and Zhou, C. F. (2004) Entorhinal deafferentation induces the expression of profilin mRNA in the reactive microglial cells in the hippocampus. Glia 47, 102-108. https://doi.org/10.1002/glia.10355
  21. Fraser, D. A., Pisalyaput, K. and Tenner, A. J. (2010) C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production. J. Neurochem. 112, 733-743. https://doi.org/10.1111/j.1471-4159.2009.06494.x
  22. Fricker, M., Neher, J. J., Zhao, J. W., Thery, C., Tolkovsky, A. M. and Brown, G. C. (2012) MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation. J. Neurosci. 32, 2657-2666. https://doi.org/10.1523/JNEUROSCI.4837-11.2012
  23. Fu, R., Shen, Q., Xu, P., Luo, J. J. and Tang, Y. (2014) Phagocytosis of microglia in the central nervous system diseases. Mol. Neurobiol. 49, 1422-1434. https://doi.org/10.1007/s12035-013-8620-6
  24. Gasque, P. (2004) Complement: a unique innate immune sensor for danger signals. Mol. Immunol. 41, 1089-1098. https://doi.org/10.1016/j.molimm.2004.06.011
  25. Ghosh, R. and Tabrizi, S. J. (2015) Clinical aspects of huntington's disease. Curr. Top. Behav. Neurosci. 22, 3-31.
  26. Gong, Y. H. and Elliott, J. L. (2000) Metallothionein expression is altered in a transgenic murine model of familial amyotrophic lateral sclerosis. Exp. Neurol. 162, 27-36. https://doi.org/10.1006/exnr.2000.7323
  27. Hanke, M. L. and Kielian, T. (2011) Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin Sci (Lond). 121, 367-387. https://doi.org/10.1042/CS20110164
  28. Hardiman, O., van den Berg, L. H. and Kiernan, M. C. (2011) Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat. Rev. Neurol. 7, 639-649
  29. Hayakawa, K., Esposito, E., Wang, X., Terasaki, Y., Liu, Y., Xing, C., Ji, X. and Lo, E. H. (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535, 551-555. https://doi.org/10.1038/nature18928
  30. Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., Lemere, C. A., Selkoe, D. J. and Stevens, B. (2016) Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712-716. https://doi.org/10.1126/science.aad8373
  31. Huang, B., Wei, W., Wang, G., Gaertig, M. A., Feng, Y., Wang, W., Li, X. J. and Li, S. (2015) Mutant huntingtin downregulates myelin regulatory factor-mediated myelin gene expression and affects mature oligodendrocytes. Neuron 85, 1212-1226. https://doi.org/10.1016/j.neuron.2015.02.026
  32. Jana, M., Palencia, C. A. and Pahan, K. (2008) Fibrillar amyloid-${\beta}$ peptides activate microglia via TLR2: implications for Alzheimer's disease. J. Immunol. 181, 7254-7262. https://doi.org/10.4049/jimmunol.181.10.7254
  33. Jansen, A. H., van Hal, M., Op den Kelder, I. C., Meier, R. T., de Ruiter, A. A., Schut, M. H., Smith, D. L., Grit, C., Brouwer, N., Kamphuis, W., Boddeke, H. W., den Dunnen, W. F., van Roon, W. M., Bates, G. P., Hol, E. M. and Reits, E. A. (2017) Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific. Glia 65, 50-61. https://doi.org/10.1002/glia.23050
  34. Jiang, R., Diaz-Castro, B., Looger, L. L. and Khakh, B. S. (2016) Dysfunctional calcium and glutamate signaling in striatal astrocytes from huntington's disease model mice. J. Neurosci. 36, 3453-3470. https://doi.org/10.1523/JNEUROSCI.3693-15.2016
  35. Jones, R. S., Minogue, A. M., Connor, T. J. and Lynch, M. A. (2013) Amyloid-${\beta}$-induced astrocytic phagocytosis is mediated by CD36, CD47 and RAGE. J. Neuroimmune Pharmacol. 8, 301-311. https://doi.org/10.1007/s11481-012-9427-3
  36. Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., Itzkovitz, S., Colonna, M., Schwartz, M. and Amit, I. (2017) A unique microglia type associated with restricting development of Alzheimer's disease. Cell 169, 1276-1290.e17. https://doi.org/10.1016/j.cell.2017.05.018
  37. Kim, J. G., Moon, M. Y., Kim, H. J., Li, Y., Song, D. K., Kim, J. S., Lee, J. Y., Kim, J., Kim, S. C. and Park, J. B. (2012) Ras-related GTPases Rap1 and RhoA collectively induce the phagocytosis of serum-opsonized zymosan particles in macrophages. J. Biol. Chem. 287, 5145-5155. https://doi.org/10.1074/jbc.M111.257634
  38. Klegeris, A., Pelech, S., Giasson, B. I., Maguire, J., Zhang, H., Mc-Geer, E. G. and McGeer, P. L. (2008) ${\alpha}$-synuclein activates stress signaling protein kinases in THP-1 cells and microglia. Neurobiol. Aging 29, 739-752. https://doi.org/10.1016/j.neurobiolaging.2006.11.013
  39. Lasiene, J. and Yamanaka, K. (2011) Glial cells in amyotrophic lateral sclerosis. Neurol. Res. Int. 2011, 718987.
  40. Lee, C. Y. and Landreth, G. E. (2010) The role of microglia in amyloid clearance from the AD brain. J Neural Transm (Vienna). 117, 949-960. https://doi.org/10.1007/s00702-010-0433-4
  41. Lee, Y. I., Li, Y., Mikesh, M., Smith, I., Nave, K. A., Schwab, M. H. and Thompson, W. J. (2016) Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions. Proc. Natl. Acad. Sci. U.S.A. 113, E479-E487. https://doi.org/10.1073/pnas.1519156113
  42. Lee, Y. J., Han, S. B., Nam, S. Y., Oh, K. W. and Hong, J. T. (2010) Inflammation and Alzheimer's disease. Arch. Pharm. Res. 33, 1539-1556. https://doi.org/10.1007/s12272-010-1006-7
  43. Lees, A. J., Hardy, J. and Revesz, T. (2009) Parkinson's disease. Lancet 373, 2055-2066. https://doi.org/10.1016/S0140-6736(09)60492-X
  44. Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Munch, A. E., Chung, W. S., Peterson, T. C., Wilton, D. K., Frouin, A., Napier, B. A., Panicker, N., Kumar, M., Buckwalter, M. S., Rowitch, D. H., Dawson, V. L., Dawson, T. M., Stevens, B. and Barres, B. A. (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481-487. https://doi.org/10.1038/nature21029
  45. Liu, S., Liu, Y., Hao, W., Wolf, L., Kiliaan, A. J., Penke, B., Rube, C. E., Walter, J., Heneka, M. T., Hartmann,T., Menger, M. D. and Fassbender, K. (2012) TLR2 is a primary receptor for Alzheimer's amyloid ${\beta}$ peptide to trigger neuroinflammatory activation. J. Immunol. 188, 1098-1107. https://doi.org/10.4049/jimmunol.1101121
  46. Lopez-Murcia, F. J., Terni, B. and Llobet, A. (2015) SPARC triggers a cell-autonomous program of synapse elimination. Proc. Natl. Acad. Sci. U.S.A. 112, 13366-13371. https://doi.org/10.1073/pnas.1512202112
  47. Matarin, M., Salih, D. A., Yasvoina, M., Cummings, D. M., Guelfi, S., Liu, W., Nahaboo Solim, M. A., Moens, T. G., Paublete, R. M., Ali, S. S., Perona, M., Desai, R., Smith, K. J., Latcham, J., Fulleylove, M., Richardson, J. C., Hardy, J. and Edwards, F. A. (2015) A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology. Cell Rep. 10, 633-644. https://doi.org/10.1016/j.celrep.2014.12.041
  48. McGeer, P. L. and McGeer, E. G. (2013) The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol. 126, 479-497. https://doi.org/10.1007/s00401-013-1177-7
  49. Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J. and Hyman, B. T. (2008) Rapid appearance and local toxicity of amyloid-${\beta}$ plaques in a mouse model of Alzheimer's disease. Nature 451, 720-724. https://doi.org/10.1038/nature06616
  50. Michelakakis, H., Xiromerisiou, G., Dardiotis, E., Bozi, M., Vassilatis, D., Kountra, P. M., Patramani, G., Moraitou, M., Papadimitriou, D., Stamboulis, E., Stefanis, L., Zintzaras, E. and Hadjigeorgiou, G. M. (2012) Evidence of an association between the scavenger receptor class B member 2 gene and Parkinson's disease. Mov. Disord. 27, 400-405. https://doi.org/10.1002/mds.24886
  51. Neher, J. J., Emmrich, J. V., Fricker, M., Mander, P. K., Thery, C. and Brown, G. C. (2013) Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc. Natl. Acad. Sci. U.S.A. 110, E4098-E4107. https://doi.org/10.1073/pnas.1308679110
  52. Nimmerjahn, A., Kirchhoff, F. and Helmchen, F. (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314-1318. https://doi.org/10.1126/science.1110647
  53. Noda, M. and Suzumura, A. (2012) Sweepers in the CNS: Microglial migration and phagocytosis in the Alzheimer disease pathogenesis. Int. J. Alzheimers Dis. 2012, 891087.
  54. Olson, J. K. and Miller, S. D. (2004) Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J. Immunol. 173, 3916-3924. https://doi.org/10.4049/jimmunol.173.6.3916
  55. Painter, M. M., Atagi, Y., Liu, C. C., Rademakers, R., Xu, H., Fryer, J. D. and Bu, G. (2015) TREM2 in CNS homeostasis and neurodegenerative disease. Mol. Neurodegener. 10, 43. https://doi.org/10.1186/s13024-015-0040-9
  56. Paolicelli, R. C. and Gross, C. T. (2011) Microglia in development: linking brain wiring to brain environment. Neuron Glia Biol. 7, 77-83. https://doi.org/10.1017/S1740925X12000105
  57. Park, J. Y., Paik, S. R., Jou, I. and Park, S. M. (2008) Microglial phagocytosis is enhanced by monomeric alpha-synuclein, not aggregated alpha-synuclein: implications for Parkinson's disease. Glia 56, 1215-1223. https://doi.org/10.1002/glia.20691
  58. Pearce, M. M., Spartz, E. J., Hong, W., Luo, L. and Kopito, R. R. (2015) Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain. Nat. Commun. 6, 6768. https://doi.org/10.1038/ncomms7768
  59. Phatnani, H. and Maniatis, T. (2015) Astrocytes in neurodegenerative disease. Cold Spring Harb Perspect Biol. 7, 1-17
  60. Philips, T. and Robberecht, W. (2011) Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 10, 253-263. https://doi.org/10.1016/S1474-4422(11)70015-1
  61. Pihlaja, R., Koistinaho, J., Malm, T., Sikkila, H., Vainio, S. and Koistinaho, M. (2008) Transplanted astrocytes internalize deposited ${\beta}$-amyloid peptides in a transgenic mouse model of Alzheimer's disease. Glia 56, 154-163. https://doi.org/10.1002/glia.20599
  62. Pomilio, C., Pavia, P., Gorojod, R. M., Vinuesa, A., Alaimo, A., Galvan, V., Kotler, M. L., Beauquis, J. and Saravia, F. (2016) Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in $A{\beta}$ internalization. Hippocampus 26, 194-210. https://doi.org/10.1002/hipo.22503
  63. Purice, M. D., Speese, S. D. and Logan, M. A. (2016) Delayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity. Nat. Commun. 7, 12871. https://doi.org/10.1038/ncomms12871
  64. Radford, R. A., Morsch, M., Rayner, S. L., Cole, N. J., Pountney, D. L. and Chung, R. S. (2015) The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia. Front Cell Neurosci. 9, 414.
  65. Rocha, S. M., Cristovao, A. C., Campos, F. L., Fonseca, C. P. and Baltazar, G. (2012) Astrocyte-derived GDNF is a potent inhibitor of microglial activation. Neurobiol. Dis. 47, 407-415. https://doi.org/10.1016/j.nbd.2012.04.014
  66. Rojanathammanee, L., Murphy, E. J. and Combs, C. K. (2011) Expression of mutant ${\alpha}$-synuclein modulates microglial phenotype in vitro. J. Neuroinflammation 8, 44. https://doi.org/10.1186/1742-2094-8-44
  67. Salminen, A., Ojala, J., Kauppinen, A., Kaarniranta, K. and Suuronen, T. (2009) Inflammation in Alzheimer's disease: amyloid-${\beta}$ oligomers trigger innate immunity defence via pattern recognition receptors. Prog. Neurobiol. 87, 181-194. https://doi.org/10.1016/j.pneurobio.2009.01.001
  68. Savage, J. C., Jay, T., Goduni, E., Quigley, C., Mariani, M. M., Malm, T., Ransohoff, R. M., Lamb, B. T. and Landreth, G. E. (2015) Nuclear receptors license phagocytosis by trem2+ myeloid cells in mouse models of Alzheimer's disease. J. Neurosci. 35, 6532-6543. https://doi.org/10.1523/JNEUROSCI.4586-14.2015
  69. Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A. and Stevens, B. (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691-705. https://doi.org/10.1016/j.neuron.2012.03.026
  70. Selkoe, D. J. and Hardy, J. (2016) The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 8, 595-608. https://doi.org/10.15252/emmm.201606210
  71. Shin, J. Y., Fang, Z. H., Yu, Z. X., Wang, C. E., Li, S. H. and Li, X. J. (2005) Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J. Cell Biol. 171, 1001-1012. https://doi.org/10.1083/jcb.200508072
  72. Sofroniew, M. V. (2015) Astrocyte barriers to neurotoxic inflammation. Nat. Rev. Neurosci. 16, 249-263. https://doi.org/10.1038/nrn3898
  73. Sofroniew, M. V. and Vinters, H. V. (2010) Astrocytes: biology and pathology. Acta Neuropathol. 119, 7-35. https://doi.org/10.1007/s00401-009-0619-8
  74. Sollvander, S., Nikitidou, E., Brolin, R., Soderberg, L., Sehlin, D., Lannfelt, L. and Erlandsson, A. (2016) Accumulation of amyloid-${\beta}$ by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol. Neurodegener. 11, 38. https://doi.org/10.1186/s13024-016-0098-z
  75. Song, J. W., Misgeld, T., Kang, H., Knecht, S., Lu, J., Cao, Y., Cotman, S. L., Bishop, D. L. and Lichtman, J. W. (2008) Lysosomal activity associated with developmental axon pruning. J. Neurosci. 28, 8993-9001. https://doi.org/10.1523/JNEUROSCI.0720-08.2008
  76. Stephan, A. H., Madison, D. V., Mateos, J. M., Fraser, D. A., Lovelett, E. A., Coutellier, L., Kim, L., Tsai, H. H., Huang, E. J., Rowitch, D. H., Berns, D. S., Tenner, A. J., Shamloo, M. and Barres, B. A. (2013) A dramatic increase of C1q protein in the CNS during normal aging. J. Neurosci. 33, 13460-13474. https://doi.org/10.1523/JNEUROSCI.1333-13.2013
  77. Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., Sher, A., Litke, A. M., Lambris, J. D., Smith, S. J., John, S. W. and Barres, B. A. (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131, 1164-1178. https://doi.org/10.1016/j.cell.2007.10.036
  78. Streit, W. J., Walter, S. A. and Pennell, N. A. (1999) Reactive microgliosis. Prog. Neurobiol. 57, 563-581. https://doi.org/10.1016/S0301-0082(98)00069-0
  79. Suh, E. C., Jung, Y. J., Kim, Y. A., Park, E. M., Lee, S. J. and Lee, K. E. (2013) Knockout of Toll-like receptor 2 attenuates $A{\beta}25$-35-induced neurotoxicity in organotypic hippocampal slice cultures. Neurochem. Int. 63, 818-825. https://doi.org/10.1016/j.neuint.2013.10.007
  80. Tahara, K., Kim, H. D., Jin, J. J., Maxwell, J. A., Li, L. and Fukuchi, K. (2006) Role of toll-like receptor signalling in $A{\beta}$ uptake and clearance. Brain 129, 3006-3019. https://doi.org/10.1093/brain/awl249
  81. Tang, S. C., Arumugam, T. V., Xu, X., Cheng, A., Mughal, M. R., Jo, D. G., Lathia, J. D., Siler, D. A., Chigurupati, S., Ouyang, X., Magnus, T., Camandola, S. and Mattson, M. P. (2007) Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc. Natl. Acad. Sci. U.S.A. 104, 13798-13803. https://doi.org/10.1073/pnas.0702553104
  82. Tasdemir-Yilmaz, O. E. and Freeman, M. R. (2014) Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. Genes Dev. 28, 20-33. https://doi.org/10.1101/gad.229518.113
  83. Terni, B., Lopez-Murcia, F. J. and Llobet, A. (2017) Role of neuron-glia interactions in developmental synapse elimination. Brain Res. Bull. 129, 74-81. https://doi.org/10.1016/j.brainresbull.2016.08.017
  84. Tong, X., Ao, Y., Faas, G. C., Nwaobi, S. E., Xu, J., Haustein, M. D., Anderson, M. A., Mody, I., Olsen, M. L., Sofroniew, M. V. and Khakh, B. S. (2014) Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice. Nat. Neurosci. 17, 694-703. https://doi.org/10.1038/nn.3691
  85. Turner, M. R., Cagnin, A., Turkheimer, F. E., Miller, C. C., Shaw, C. E., Brooks, D. J., Leigh, P. N. and Banati, R. B. (2004) Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol. Dis. 15, 601-609. https://doi.org/10.1016/j.nbd.2003.12.012
  86. Ulland, T. K., Song, W. M., Huang, S. C., Ulrich, J. D., Sergushichev, A., Beatty, W. L., Loboda, A. A., Zhou, Y., Cairns, N. J., Kambal, A., Loginicheva, E., Gilfillan, S., Cella, M., Virgin, H. W., Unanue, E. R., Wang, Y., Artyomov, M. N., Holtzman, D. M. and Colonna, M. (2017) TREM2 maintains microglial metabolic fitness in Alzheimer's disease. Cell 170, 649-663.e13. https://doi.org/10.1016/j.cell.2017.07.023
  87. Ulrich, J. D. and Holtzman, D. M. (2016) TREM2 function in Alzheimer's disease and neurodegeneration. ACS Chem. Neurosci. 7, 420-427. https://doi.org/10.1021/acschemneuro.5b00313
  88. Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., Holtzman, D. M., Cirrito, J. R. and Colonna, M. (2015) TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell 160, 1061-1071. https://doi.org/10.1016/j.cell.2015.01.049
  89. Weydt, P., Yuen, E. C., Ransom, B. R. and Moller, T. (2004) Increased cytotoxic potential of microglia from ALS-transgenic mice. Glia 48, 179-182. https://doi.org/10.1002/glia.20062
  90. Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C. and Husemann, J. (2003) Adult mouse astrocytes degrade amyloid-${\beta}$ in vitro and in situ. Nat. Med. 9, 453-457. https://doi.org/10.1038/nm838
  91. Yamanaka, K., Chun, S. J., Boillee, S., Fujimori-Tonou, N., Yamashita, H., Gutmann, D. H., Takahashi, R., Misawa, H. and Cleveland, D. W. (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci. 11, 251-253. https://doi.org/10.1038/nn2047
  92. Yang, J., Yang, H., Liu, Y., Li, X., Qin, L., Lou, H., Duan, S. and Wang, H. (2016a) Astrocytes contribute to synapse elimination via type 2 inositol 1,4,5-trisphosphate receptor-dependent release of ATP. Elife 5, e15043.
  93. Yang, L., Liu, C. C., Zheng, H., Kanekiyo, T., Atagi, Y., Jia, L., Wang, D., N'Songo, A., Can, D., Xu, H., Chen, X. F. and Bu, G. (2016b) LRP1 modulates the microglial immune response via regulation of JNK and NF-${\kappa}B$ signaling pathways. J. Neuroinflammation 13, 304. https://doi.org/10.1186/s12974-016-0772-7
  94. Zhang, B., Tian, M., Zheng, H., Zhen, Y., Yue, Y., Li, T., Li, S., Marcantonio, E. R. and Xie, Z. (2013) Effects of anesthetic isoflurane and desflurane on human cerebrospinal fluid $A{\beta}$ and ${\tau}$ level. Anesthesiology 119, 52-60. https://doi.org/10.1097/ALN.0b013e31828ce55d
  95. Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., Deng, S., Liddelow, S. A., Zhang, C., Daneman, R., Maniatis, T., Barres, B. A. and Wu, J. Q. (2014) An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929-11947. https://doi.org/10.1523/JNEUROSCI.1860-14.2014

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