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Annual Review of Physiology

Volume 79, 2017

Microglia in Physiology and Disease

Abstract

As the immune-competent cells of the brain, microglia play an increasingly important role in maintaining normal brain function. They invade the brain early in development, transform into a highly ramified phenotype, and constantly screen their environment. Microglia are activated by any type of pathologic event or change in brain homeostasis. This activation process is highly diverse and depends on the context and type of the stressor or pathology. Microglia can strongly influence the pathologic outcome or response to a stressor due to the release of a plethora of substances, including cytokines, chemokines, and growth factors. They are the professional phagocytes of the brain and help orchestrate the immunological response by interacting with infiltrating immune cells. We describe here the diversity of microglia phenotypes and their responses in health, aging, and disease. We also review the current literature about the impact of lifestyle on microglia responses and discuss treatment options that modulate microglial phenotypes.

Keyword(s): aging, brain macrophages, immune responses, neurodegeneration, pathology, phagocytosis, priming, synaptic pruning
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/content/journals/10.1146/annurev-physiol-022516-034406
2017-02-10
2024-04-19
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Literature Cited

  1. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. 1.  2011. Physiology of microglia. Physiol. Rev. 91:461–553 [Google Scholar]
  2. Sierra A, Beccari S, Diaz-Aparicio I, Encinas JM, Comeau S, Tremblay MÈ. 2.  2014. Surveillance, phagocytosis, and inflammation: how never-resting microglia influence adult hippocampal neurogenesis. Neural Plast. 2014:610343 [Google Scholar]
  3. Virchow R. 3.  1856. Gesammelte Abhandlungen zur wissenschaftlichen Medicin Frankfurt, Ger.: Verlag von Meidinger Sohn & Comp.
  4. Weigert C. 4.  1895. Beiträge zur Kenntnis der Normalen Menschlichen Glia Frankfurt: Verlag Moritz Diesterweg
  5. 5. Lenhossek 1895. Bau des Nervensystems Berlin: Fischer Verlag
  6. Cajal RY. 6.  1897. Algo sobre la significación fisiológica de la neuroglía. Rev. Trimest. Microgr. 2:33–47 [Google Scholar]
  7. Alzheimer A. 7.  1910. Beiträge zur Kenntnis der pathologischen Neuroglia und ihrer Beziehungen zu den Abbauvorgängen im Nervengewebe. Histologische und Histopathologische Arbeiten über die Grosshirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie der Geisteskrankheiten F Nissl, A Alzheimer 401–562 Jena, Ger.: Verlag Gustav Fischer [Google Scholar]
  8. Nissl F. 8.  1904. Über einige Beziehungen zwischen Nervenzellenerkrankungen und gliösen Erscheinungen bei verschiedenen Psychosen. Arch Psych 32:1–21 [Google Scholar]
  9. Sierra A, de Castro F, Río-Hortega J, Iglesias-Rozas J, Garrosa M, Kettenmann H. 9.  2016. The “big-bang” for modern glial biology: translation and comments on Pío del Río-Hortega 1919 series of papers on microglia. Glia 64:1801–40 [Google Scholar]
  10. Blinzinger K, Kreutzberg G. 10.  1968. Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z. Zellforsch. Mikrosk. Anat. 85:145–57 [Google Scholar]
  11. Hoeffel G, Ginhoux F. 11.  2015. Ontogeny of tissue-resident macrophages. Front. Immunol. 6:486 [Google Scholar]
  12. Ginhoux F, Prinz M. 12.  2015. Origin of microglia: current concepts and past controversies. Cold Spring Harb. Perspect. Biol. 7:a020537 [Google Scholar]
  13. Katsumoto A, Lu H, Miranda AS, Ransohoff RM. 13.  2014. Ontogeny and functions of central nervous system macrophages. J. Immunol. 193:2615–21 [Google Scholar]
  14. Prinz M, Priller J. 14.  2014. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat. Rev. Neurosci. 15:300–12 [Google Scholar]
  15. Nayak D, Roth TL, McGavern DB. 15.  2014. Microglia development and function. Annu. Rev. Immunol. 32:367–402 [Google Scholar]
  16. Bilimoria PM, Stevens B. 16.  2015. Microglia function during brain development: new insights from animal models. Brain Res 1617:7–17 [Google Scholar]
  17. Filiano AJ, Gadani SP, Kipnis J. 17.  2015. Interactions of innate and adaptive immunity in brain development and function. Brain Res 1617:18–27 [Google Scholar]
  18. Michell-Robinson MA, Touil H, Healy LM, Owen DR, Durafourt BA. 18.  et al. 2015. Roles of microglia in brain development, tissue maintenance and repair. Brain 138:1138–59 [Google Scholar]
  19. Derecki NC, Katzmarski N, Kipnis J, Meyer-Luehmann M. 19.  2014. Microglia as a critical player in both developmental and late-life CNS pathologies. Acta Neuropathol 128:333–45 [Google Scholar]
  20. Guizzetti M, Zhang X, Goeke C, Gavin DP. 20.  2014. Glia and neurodevelopment: focus on fetal alcohol spectrum disorders. Front. Pediatr. 2:123 [Google Scholar]
  21. Hristovska I, Pascual O. 21.  2015. Deciphering resting microglial morphology and process motility from a synaptic prospect. Front. Integr. Neurosci. 9:73 [Google Scholar]
  22. Hong S, Dissing-Olesen L, Stevens B. 22.  2016. New insights on the role of microglia in synaptic pruning in health and disease. Curr. Opin. Neurobiol. 36:128–34 [Google Scholar]
  23. Siskova Z, Tremblay ME. 23.  2013. Microglia and synapse: interactions in health and neurodegeneration. Neural Plast. 2013:425845 [Google Scholar]
  24. Kettenmann H, Kirchhoff F, Verkhratsky A. 24.  2013. Microglia: new roles for the synaptic stripper. Neuron 77:10–18 [Google Scholar]
  25. Su P, Zhang J, Zhao F, Aschner M, Chen J, Luo W. 25.  2014. The interaction between microglia and neural stem/precursor cells. Brain Res Bull 109:32–38 [Google Scholar]
  26. Habib P, Beyer C. 26.  2015. Regulation of brain microglia by female gonadal steroids. J. Steroid Biochem. Mol. Biol. 146:3–14 [Google Scholar]
  27. Lenz KM, McCarthy MM. 27.  2015. A starring role for microglia in brain sex differences. Neuroscientist 21:306–21 [Google Scholar]
  28. Smith AM, Dragunow M. 28.  2014. The human side of microglia. Trends Neurosci 37:125–35 [Google Scholar]
  29. Streit WJ, Xue QS, Tischer J, Bechmann I. 29.  2014. Microglial pathology. Acta Neuropathol. Commun. 2:142 [Google Scholar]
  30. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ. 30.  et al. 2014. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci. 17:131–43 [Google Scholar]
  31. Linnartz-Gerlach B, Mathews M, Neumann H. 31.  2014. Sensing the neuronal glycocalyx by glial sialic acid binding immunoglobulin-like lectins. Neuroscience 275:113–24 [Google Scholar]
  32. Beins E, Ulas T, Ternes S, Neumann H, Schultze JL, Zimmer A. 32.  2016. Characterization of inflammatory markers and transcriptome profiles of differentially activated embryonic stem cell-derived microglia. Glia 64:1007–20 [Google Scholar]
  33. Muffat J, Li Y, Yuan B, Mitalipova M, Omer A. 33.  et al. 2016. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med. 22:1358–67 [Google Scholar]
  34. Gertig U, Hanisch UK. 34.  2014. Microglial diversity by responses and responders. Front. Cell. Neurosci. 8:101 [Google Scholar]
  35. Wogram E, Wendt S, Matyash M, Pivneva T, Draguhn A, Kettenmann H. 35.  2016. Satellite microglia show spontaneous electrical activity that is uncorrelated with activity of the attached neuron. Eur. J. Neurosci. 43:1523–34 [Google Scholar]
  36. Baalman K, Marin MA, Ho TS, Godoy M, Cherian L. 36.  et al. 2015. Axon initial segment-associated microglia. J. Neurosci. 35:2283–92 [Google Scholar]
  37. Ribeiro Xavier AL, Kress BT, Goldman SA, Lacerda de Menezes JR, Nedergaard M. 37.  2015. A distinct population of microglia supports adult neurogenesis in the subventricular zone. J. Neurosci. 35:11848–61 [Google Scholar]
  38. Seifert S, Pannell M, Uckert W, Farber K, Kettenmann H. 38.  2011. Transmitter- and hormone-activated Ca2+ responses in adult microglia/brain macrophages in situ recorded after viral transduction of a recombinant Ca2+ sensor. Cell Calcium 49:365–75 [Google Scholar]
  39. Pannell M, Meier MA, Szulzewsky F, Matyash V, Endres M. 39.  et al. 2016. The subpopulation of microglia expressing functional muscarinic acetylcholine receptors expands in stroke and Alzheimer's disease. Brain Struct. Funct. 221:1157–72 [Google Scholar]
  40. Pannell M, Szulzewsky F, Matyash V, Wolf SA, Kettenmann H. 40.  2014. The subpopulation of microglia sensitive to neurotransmitters/neurohormones is modulated by stimulation with LPS, interferon-γ, and IL-4. Glia 62:667–79 [Google Scholar]
  41. Grabert K, Michoel T, Karavolos MH, Clohisey S, Baillie JK. 41.  et al. 2016. Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat. Neurosci. 19:504–16 [Google Scholar]
  42. Hanisch UK, Kettenmann H. 42.  2007. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10:1387–94 [Google Scholar]
  43. Tang Y, Le W. 43.  2016. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 53:1181–94 [Google Scholar]
  44. Orihuela R, McPherson CA, Harry GJ. 44.  2016. Microglial M1/M2 polarization and metabolic states. Br. J. Pharmacol. 173:649–65 [Google Scholar]
  45. Franco R, Fernández-Suárez D. 45.  2015. Alternatively activated microglia and macrophages in the central nervous system. Prog. Neurobiol. 131:65–86 [Google Scholar]
  46. Greter M, Lelios I, Croxford AL. 46.  2015. Microglia versus myeloid cell nomenclature during brain inflammation. Front. Immunol. 6:249 [Google Scholar]
  47. Cherry JD, Olschowka JA, O'Banion MK. 47.  2014. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J. Neuroinflamm. 11:98 [Google Scholar]
  48. Cherry JD, Olschowka JA, O'Banion MK. 48.  2014. Are “resting” microglia more “M2”?. Front. Immunol. 5:594 [Google Scholar]
  49. Chen Z, Trapp BD. 49.  2016. Microglia and neuroprotection. J. Neurochem. 136:Suppl. 110–17 [Google Scholar]
  50. Biber K, Owens T, Boddeke E. 50.  2014. What is microglia neurotoxicity (not)?. Glia 62:841–54 [Google Scholar]
  51. Wieghofer P, Knobeloch KP, Prinz M. 51.  2015. Genetic targeting of microglia. Glia 63:1–22 [Google Scholar]
  52. Waisman A, Ginhoux F, Greter M, Bruttger J. 52.  2015. Homeostasis of microglia in the adult brain: review of novel microglia depletion systems. Trends Immunol 36:625–36 [Google Scholar]
  53. Liu GJ, Middleton RJ, Hatty CR, Kam WW, Chan R. 53.  et al. 2014. The 18 kDa translocator protein, microglia and neuroinflammation. Brain Pathol. 24:631–53 [Google Scholar]
  54. Crotti A, Ransohoff RM. 54.  2016. Microglial physiology and pathophysiology: insights from genome-wide transcriptional profiling. Immunity 44:505–15 [Google Scholar]
  55. Wes PD, Holtman IR, Boddeke EW, Möller T, Eggen BJ. 55.  2016. Next generation transcriptomics and genomics elucidate biological complexity of microglia in health and disease. Glia 64:197–213 [Google Scholar]
  56. Su P, Zhang J, Wang D, Zhao F, Cao Z. 56.  et al. 2016. The role of autophagy in modulation of neuroinflammation in microglia. Neuroscience 319:155–67 [Google Scholar]
  57. Cardoso AL, Guedes JR, de Lima MC. 57.  2016. Role of microRNAs in the regulation of innate immune cells under neuroinflammatory conditions. Curr. Opin. Pharmacol. 26:1–9 [Google Scholar]
  58. Gautier EL, Shay T, Miller J, Greter M, Jakubzick C. 58.  et al. 2012. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat. Immunol. 13:1118–28 [Google Scholar]
  59. Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC. 59.  et al. 2013. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci 16:1896–905 [Google Scholar]
  60. Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR. 60.  et al. 2014. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci 34:11929–47 [Google Scholar]
  61. Holtman IR, Noback M, Bijlsma M, Duong KN, van der Geest MA. 61.  et al. 2015. Glia Open Access Database (GOAD): a comprehensive gene expression encyclopedia of glia cells in health and disease. Glia 63:1495–506 [Google Scholar]
  62. Zeisel A, Munoz-Manchado AB, Codeluppi S, Lonnerberg P, La Manno G. 62.  et al. 2015. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347:1138–42 [Google Scholar]
  63. Gosselin D, Link VM, Romanoski CE, Fonseca GJ, Eichenfield DZ. 63.  et al. 2014. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159:1327–40 [Google Scholar]
  64. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H. 64.  et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:1312–26 [Google Scholar]
  65. Su W, Aloi MS, Garden GA. 65.  2016. MicroRNAs mediating CNS inflammation: small regulators with powerful potential. Brain Behav. Immun. 52:1–8 [Google Scholar]
  66. Hambardzumyan D, Gutmann DH, Kettenmann H. 66.  2016. The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci. 19:20–27 [Google Scholar]
  67. Glass R, Synowitz M. 67.  2014. CNS macrophages and peripheral myeloid cells in brain tumours. Acta Neuropathol 128:347–62 [Google Scholar]
  68. Szulzewsky F, Arora S, de Witte L, Ulas T, Wolf S, Kettenmann H. 68.  2016. Human glioblastoma-associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples. Glia 64:1416–36 [Google Scholar]
  69. Bogie JF, Stinissen P, Hendriks JJ. 69.  2014. Macrophage subsets and microglia in multiple sclerosis. Acta Neuropathol. 128:191–213 [Google Scholar]
  70. Giunti D, Parodi B, Cordano C, Uccelli A, Kerlero de Rosbo N. 70.  2014. Can we switch microglia's phenotype to foster neuroprotection? Focus on multiple sclerosis. Immunology 141:328–39 [Google Scholar]
  71. Chen X, Ma X, Jiang Y, Pi R, Liu Y, Ma L. 71.  2011. The prospects of minocycline in multiple sclerosis.. J. Neuroimmunol 235:1–8 [Google Scholar]
  72. Savitz SI, Cox CS Jr.. 72.  2016. Concise review: cell therapies for stroke and traumatic brain injury: targeting microglia. Stem Cells 34:537–42 [Google Scholar]
  73. Fumagalli S, Perego C, Pischiutta F, Zanier ER, De Simoni MG. 73.  2015. The ischemic environment drives microglia and macrophage function. Front. Neurol. 6:81 [Google Scholar]
  74. Benakis C, Garcia-Bonilla L, Iadecola C, Anrather J. 74.  2014. The role of microglia and myeloid immune cells in acute cerebral ischemia. Front. Cell. Neurosci. 8:461 [Google Scholar]
  75. Lee Y, Lee SR, Choi SS, Yeo HG, Chang KT, Lee HJ. 75.  2014. Therapeutically targeting neuroinflammation and microglia after acute ischemic stroke. Biomed. Res. Int. 2014:297241 [Google Scholar]
  76. Perry VH, Holmes C. 76.  2014. Microglial priming in neurodegenerative disease. Nat. Rev. Neurol. 10:217–24 [Google Scholar]
  77. Norden DM, Godbout JP. 77.  2013. Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol. Appl. Neurobiol. 39:19–34 [Google Scholar]
  78. Holtman IR, Raj DD, Miller JA, Schaafsma W, Yin Z. 78.  et al. 2015. Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis. Acta Neuropathol Commun 3:31 [Google Scholar]
  79. Heneka MT, Kummer MP, Latz E. 79.  2014. Innate immune activation in neurodegenerative disease. Nat. Rev. Immunol. 14:463–77 [Google Scholar]
  80. Doty KR, Guillot-Sestier MV, Town T. 80.  2015. The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?. Brain Res. 1617:155–73 [Google Scholar]
  81. Ransohoff RM, El Khoury J. 81.  2016. Microglia in health and disease. Cold Spring Harb. Perspect. Biol. 8a020560
  82. Santoni G, Cardinali C, Morelli MB, Santoni M, Nabissi M, Amantini C. 82.  2015. Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J. Neuroinflamm. 12:21 [Google Scholar]
  83. Lehnardt S. 83.  2010. Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia 58:253–63 [Google Scholar]
  84. Strowig T, Henao-Mejia J, Elinav E, Flavell R. 84.  2012. Inflammasomes in health and disease. Nature 481:278–86 [Google Scholar]
  85. Heppner FL, Ransohoff RM, Becher B. 85.  2015. Immune attack: the role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 16:358–72 [Google Scholar]
  86. Malik M, Parikh I, Vasquez JB, Smith C, Tai L. 86.  et al. 2015. Genetics ignite focus on microglial inflammation in Alzheimer's disease. Mol. Neurodegener. 10:52 [Google Scholar]
  87. ElAli A, Rivest S. 87.  2015. Microglia in Alzheimer's disease: a multifaceted relationship. Brain Behav. Immun.
  88. Gold M, El Khoury J. 88.  2015. β-Amyloid, microglia, and the inflammasome in Alzheimer's disease. Semin. Immunopathol. 37:607–11 [Google Scholar]
  89. Zhang B, Gaiteri C, Bodea LG, Wang Z, McElwee J. 89.  et al. 2013. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 153:707–20 [Google Scholar]
  90. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S. 90.  et al. 2013. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493:674–78 [Google Scholar]
  91. Krabbe G, Halle A, Matyash V, Rinnenthal JL, Eom GD. 91.  et al. 2013. Functional impairment of microglia coincides with Beta-amyloid deposition in mice with Alzheimer-like pathology. PLOS ONE 8:e60921 [Google Scholar]
  92. Brites D, Vaz AR. 92.  2014. Microglia centered pathogenesis in ALS: insights in cell interconnectivity. Front. Cell. Neurosci. 8:117 [Google Scholar]
  93. Surendranathan A, Rowe JB, O'Brien JT. 93.  2015. Neuroinflammation in Lewy body dementia. Parkinsonism Relat. Disord. 21:1398–406 [Google Scholar]
  94. Schapansky J, Nardozzi JD, LaVoie MJ. 94.  2015. The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease. Neuroscience 302:74–88 [Google Scholar]
  95. Radford RA, Morsch M, Rayner SL, Cole NJ, Pountney DL, Chung RS. 95.  2015. The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia. Front. Cell. Neurosci. 9:414 [Google Scholar]
  96. Machado V, Zöller T, Attaai A, Spittau B. 96.  2016. Microglia-mediated neuroinflammation and neurotrophic factor-induced protection in the MPTP mouse model of Parkinson's disease-lessons from transgenic mice. Int. J. Mol. Sci. 17: In press. https://doi.org/10.3390/ijms17020151 [Google Scholar]
  97. Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I. 97.  et al. 2013. Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLOS ONE 8:e55375 [Google Scholar]
  98. Streit WJ, Xue QS. 98.  2014. Human CNS immune senescence and neurodegeneration. Curr. Opin. Immunol. 29:93–96 [Google Scholar]
  99. Ojo JO, Rezaie P, Gabbott PL, Stewart MG. 99.  2015. Impact of age-related neuroglial cell responses on hippocampal deterioration. Front. Aging Neurosci. 7:57 [Google Scholar]
  100. Damani MR, Zhao L, Fontainhas AM, Amaral J, Fariss RN, Wong WT. 100.  2011. Age-related alterations in the dynamic behavior of microglia. Aging Cell 10:263–76 [Google Scholar]
  101. van Ham TJ, Brady CA, Kalicharan RD, Oosterhof N, Kuipers J. 101.  et al. 2014. Intravital correlated microscopy reveals differential macrophage and microglial dynamics during resolution of neuroinflammation. Dis. Model. Mech. 7:857–69 [Google Scholar]
  102. Petrelli F, Pucci L, Bezzi P. 102.  2016. Astrocytes and microglia and their potential link with autism spectrum disorders. Front. Cell. Neurosci. 10:21 [Google Scholar]
  103. Estes ML, McAllister AK. 103.  2015. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat. Rev. Neurosci. 16:469–86 [Google Scholar]
  104. Koyama R, Ikegaya Y. 104.  2015. Microglia in the pathogenesis of autism spectrum disorders. Neurosci. Res. 100:1–5 [Google Scholar]
  105. Takano T. 105.  2015. Role of microglia in autism: recent advances. Dev. Neurosci. 37:195–202 [Google Scholar]
  106. Zantomio D, Chana G, Laskaris L, Testa R, Everall I. 106.  et al. 2015. Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD. Neurosci. Biobehav. Rev. 52:172–77 [Google Scholar]
  107. Theoharides TC, Athanassiou M, Panagiotidou S, Doyle R. 107.  2015. Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders. J. Neuroimmunol 279:33–38 [Google Scholar]
  108. Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB. 108.  et al. 2012. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484:105–9 [Google Scholar]
  109. Wang J, Wegener JE, Huang TW, Sripathy S, De Jesus-Cortes H. 109.  et al. 2015. Wild-type microglia do not reverse pathology in mouse models of Rett syndrome. Nature 521:E1–4 [Google Scholar]
  110. Werling DM, Parikshak NN, Geschwind DH. 110.  2016. Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. Nature Comm. 7:10717 [Google Scholar]
  111. Leza JC, Garcia-Bueno B, Bioque M, Arango C, Parellada M. 111.  et al. 2015. Inflammation in schizophrenia: a question of balance. Neurosci. Biobehav. Rev. 55:612–26 [Google Scholar]
  112. Watkins DC, Assari S, Johnson-Lawrence V. 112.  2015. Race and ethnic group differences in comorbid major depressive disorder, generalized anxiety disorder, and chronic medical conditions. J. Racial Ethn. Health Disparities 2:385–94 [Google Scholar]
  113. Watkins CC, Sawa A, Pomper MG. 113.  2014. Glia and immune cell signaling in bipolar disorder: insights from neuropharmacology and molecular imaging to clinical application. Transl. Psychiatry 4:e350 [Google Scholar]
  114. Stertz L, Magalhaes PV, Kapczinski F. 114.  2013. Is bipolar disorder an inflammatory condition? The relevance of microglial activation. Curr. Opin. Psychiatry 26:19–26 [Google Scholar]
  115. Ascoli BM, Gea LP, Colombo R, Barbe-Tuana FM, Kapczinski F, Rosa AR. 115.  2016. The role of macrophage polarization on bipolar disorder: identifying new therapeutic targets. Aust. N.Z. J. Psychiatry 50:618–30 [Google Scholar]
  116. Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR. 116.  et al. 2016. Schizophrenia risk from complex variation of complement component 4. Nature 530:177–83 [Google Scholar]
  117. Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. 117.  2016. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology 233:1637–50 [Google Scholar]
  118. Delpech JC, Madore C, Nadjar A, Joffre C, Wohleb ES, Laye S. 118.  2015. Microglia in neuronal plasticity: influence of stress. Neuropharmacology 96:19–28 [Google Scholar]
  119. Herrera AJ, Espinosa-Oliva AM, Carrillo-Jiménez A, Oliva-Martín MJ, García-Revilla J. 119.  et al. 2015. Relevance of chronic stress and the two faces of microglia in Parkinson's disease. Front. Cell. Neurosci. 9:312 [Google Scholar]
  120. Reader BF, Jarrett BL, McKim DB, Wohleb ES, Godbout JP, Sheridan JF. 120.  2015. Peripheral and central effects of repeated social defeat stress: monocyte trafficking, microglial activation, and anxiety. Neuroscience 289:429–42 [Google Scholar]
  121. Walker FR, Nilsson M, Jones K. 121.  2013. Acute and chronic stress-induced disturbances of microglial plasticity, phenotype and function. Curr. Drug Targets 14:1262–76 [Google Scholar]
  122. Bellavance MA, Rivest S. 122.  2014. The HPA-immune axis and the immunomodulatory actions of glucocorticoids in the brain. Front. Immunol. 5:136 [Google Scholar]
  123. Bolton JL, Bilbo SD. 123.  2014. Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms. Dialogues Clin. Neurosci. 16:307–20 [Google Scholar]
  124. Hale MW, Spencer SJ, Conti B, Jasoni CL, Kent S. 124.  et al. 2015. Diet, behavior and immunity across the lifespan. Neurosci. Biobehav. Rev. 58:46–62 [Google Scholar]
  125. Forsythe P. 125.  2016. Microbes taming mast cells: implications for allergic inflammation and beyond. Eur. J. Pharmacol. 778:169–75 [Google Scholar]
  126. de Git KC, Adan RA. 126.  2015. Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation. Obes. Rev. 16:207–24 [Google Scholar]
  127. Valdearcos M, Xu AW, Koliwad SK. 127.  2015. Hypothalamic inflammation in the control of metabolic function. Annu. Rev. Physiol. 77:131–60 [Google Scholar]
  128. Wu Z, Yu J, Zhu A, Nakanishi H. 128.  2016. Nutrients, microglia aging, and brain aging. Oxid. Med. Cell. Longev. 2016:7498528 [Google Scholar]
  129. Kalin S, Heppner FL, Bechmann I, Prinz M, Tschop MH, Yi CX. 129.  2015. Hypothalamic innate immune reaction in obesity. Nat. Rev. Endocrinol. 11:339–51 [Google Scholar]
  130. Chastain LG, Sarkar DK. 130.  2014. Role of microglia in regulation of ethanol neurotoxic action. Int. Rev. Neurobiol. 118:81–103 [Google Scholar]
  131. Crews FT, Vetreno RP. 131.  2014. Neuroimmune basis of alcoholic brain damage. Int. Rev. Neurobiol. 118:315–57 [Google Scholar]
  132. Wilhelm CJ, Guizzetti M. 132.  2015. Fetal alcohol spectrum disorders: an overview from the glia perspective. Front. Integr. Neurosci. 9:65 [Google Scholar]
  133. Crews FT, Vetreno RP. 133.  2016. Mechanisms of neuroimmune gene induction in alcoholism. Psychopharmacology 233:1543–57 [Google Scholar]
  134. Gorky J, Schwaber J. 134.  2016. The role of the gut-brain axis in alcohol use disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 65:234–41 [Google Scholar]
  135. Möller T, Boddeke HW. 135.  2016. Glial cells as drug targets: What does it take?. Glia 64:1742–54 [Google Scholar]
  136. Valero J, Paris I, Sierra A. 136.  2016. Lifestyle shapes the dialogue between environment, microglia, and adult neurogenesis. ACS Chem. Neurosci. 7:442–53 [Google Scholar]
  137. Ingiosi AM, Opp MR, Krueger JM. 137.  2013. Sleep and immune function: glial contributions and consequences of aging. Curr. Opin. Neurobiol. 23:806–11 [Google Scholar]
  138. Svensson M, Lexell J, Deierborg T. 138.  2015. Effects of physical exercise on neuroinflammation, neuroplasticity, neurodegeneration, and behavior: what we can learn from animal models in clinical settings. Neurorehabil. Neural Repair 29:577–89 [Google Scholar]
  139. Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA. 139.  2015. Protective effects of ginseng on neurological disorders. Front. Aging Neurosci. 7:129 [Google Scholar]
  140. El-Sayyad HI. 140.  2015. Cholesterol overload impairing cerebellar function: the promise of natural products. Nutrition 31:621–30 [Google Scholar]
  141. McNamara RK, Vannest JJ, Valentine CJ. 141.  2015. Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: mechanisms and implications for psychopathology. World J. Psychiatry 5:15–34 [Google Scholar]
  142. Morgan TE, Wong AM, Finch CE. 142.  2007. Anti-inflammatory mechanisms of dietary restriction in slowing aging processes. Interdiscip. Top. Gerontol. 35:83–97 [Google Scholar]
  143. Dobson JL, McMillan J, Li L. 143.  2014. Benefits of exercise intervention in reducing neuropathic pain. Front. Cell. Neurosci. 8:102 [Google Scholar]
  144. Singhal G, Jaehne EJ, Corrigan F, Baune BT. 144.  2014. Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment. Front. Cell. Neurosci. 8:97 [Google Scholar]
/content/journals/10.1146/annurev-physiol-022516-034406
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Microglia in Physiology and Disease
Annual Review of Physiology 79, 619 (2017); https://doi.org/10.1146/annurev-physiol-022516-034406
/content/journals/10.1146/annurev-physiol-022516-034406
/content/journals/10.1146/annurev-physiol-022516-034406
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  • Article Type: Review Article

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