Astrocytes and microglia and their potential link with autism spectrum disorders

Frontiers in Cellular Neuroscience

Volumn 10, Issue FEB, 2016, Pages

  Petrelli, Francesco ^a   Pucci, Luca ^a   Bezzi, Paola ^a  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

Astrocytes; Autism spectrum disorders (ASD); Microglia; Neurosciences

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CARTILAGE OLIGOMERIC MATRIX PROTEIN; CHEMOKINE RECEPTOR CX3CR1; COMPLEMENT COMPONENT C3 RECEPTOR; DEXTRO SERINE; FATTY ACID BINDING PROTEIN; G PROTEIN COUPLED RECEPTOR; GLUTAMATE RECEPTOR; GLUTATHIONE TRANSFERASE A1; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; MEGF10 PROTEIN; MERTK RECEPTOR; METHYL CPG BINDING PROTEIN 2; NEUROTRANSMITTER; PROTEIN TYROSINE KINASE; THROMBOSPONDIN 1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ARTICLE; ASTROCYTE; AUTISM; CELL COMMUNICATION; CELL MATURATION; COGNITIVE DEFECT; CYTOKINE RELEASE; EXCITATORY POSTSYNAPTIC POTENTIAL; GLIA CELL; HUMAN; MICROGLIA; NERVE CELL MEMBRANE POTENTIAL; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PATHOGENESIS; PROTEIN PROTEIN INTERACTION; RETT SYNDROME; SINGLE NUCLEOTIDE POLYMORPHISM; SYNAPTIC POTENTIAL; SYNAPTIC TRANSMISSION; SYNAPTOGENESIS;

EID: 84958747299     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2016.00021     Document Type: Article

References (115)

1. Abrahams, B. S., and Geschwind, D. H. (2008). Advances in autism genetics: on the threshold of a new neurobiology. Nat. Rev. Genet. 9, 341-355. doi: 10.1038/nrg2346.
2. Allen, N. J., Bennett, M. L., Foo, L. C., Wang, G. X., Chakraborty, C., Smith, S. J., et al. (2012). Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature 486, 410-414. doi: 10.1038/nature11059.
3. Araque, A., Carmignoto, G., Haydon, P. G., Oliet, S. H. R., Robitaille, R., and Volterra, A. (2014). Gliotransmitters travel in time and space. Neuron 81, 728-739. doi: 10.1016/j.neuron.2014.02.007.
4. Atladottir, H. O., Pedersen, M. G., Thorsen, P., Mortensen, P. B., Deleuran, B., Eaton, W. W., et al. (2009). Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 124, 687-694. doi: 10.1542/peds.2008-2445.
5. Bailey, A., Lecouteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., et al. (1995). Autism as a strongly genetic disorder - evidence from a british twin study.Psychol. Med. 25, 63-77. doi: 10.1017/S0033291700028099.
6. Bailey-Bucktrout, S. L., Caulkins, S. C., Goings, G., Fischer, J. A. A., Dzionek, A., and Miller, S. D. (2008). Central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis. J. Immunol. 180, 6457-6461. doi: 10.4049/jimmunol.180.10.6457.
7. Ballas, N., Lioy, D. T., Grunseich, C., and Mandel, G. (2009). Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat. Neurosci.12, 311-317. doi: 10.1038/nn.2275.
8. Barnby, G., Abbott, A., Sykes, N., Morris, A., Weeks, D. E., Mott, R., et al. (2005). Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT. Am. J. Hum. Genet. 76, 950-966. doi: 10.1086/430454.
9. Barres, B. A. (2008). The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60, 430-440. doi: 10.1016/j.neuron.2008.10.013.
10. Bezzi, P., Domercq, M., Brambilla, L., Galli, R., Schols, D., De Clercq, E., et al. (2001). CXCR4-activated astrocyte glutamate release via TNFa: amplification by microglia triggers neurotoxicity. Nat. Neurosci. 4, 702-710. doi: 10.1038/89490.
11. Bezzi, P., and Volterra, A. (2001). A neuron-glia signalling network in the active brain.Curr. Opin. Neurobiol. 11, 387-394. doi: 10.1016/S0959-4388(00)00223-3.
12. Bhat, S. S., Ladd, S., Grass, F., Spence, J. E., Brasington, C. K., Simensen, R. J., et al. (2008). Disruption of the IL1RAPL1 gene associated with a pericentromeric inversion of the X chromosome in a patient with mental retardation and autism. Clin. Genet. 73, 94-96. doi: 10.1111/j.1399-0004.2007.00920.x.
13. Bucan, M., Abrahams, B. S., Wang, K., Glessner, J. T., Herman, E. I., Sonnenblick, L. I., et al. (2009). Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genet. 5:e1000536. doi: 10.1371/journal.pgen.1000536.
14. Bulloch, K., Miller, M. M., Gal-Toth, J., Milner, T. A., Gottfried-Blackmore, A., Waters, E. M., et al. (2008). CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain. J. Compar. Neurol. 508, 687-710. doi: 10.1002/cne.21668.
15. Bushong, E. A., Martone, M. E., Jones, Y. Z., and Ellisman, M. H. (2002). Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci.22, 183-192.
16. Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., et al. (2008). A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264-278. doi: 10.1523/JNEUROSCI.4178-07.2008.
17. Carson, M. J., Bilousova, T. V., Puntambekar, S. S., Melchior, B., Doose, J. M., and Ethell, I. M. (2007). A rose by any other name? The potential consequences of microglial heterogeneity during CNS health and disease. Neurotherapeutics 4, 571-579. doi: 10.1016/j.nurt.2007.07.002.
18. Chahrour, M., and Zoghbi, H. Y. (2007). The story of rett syndrome: from clinic to neurobiology. Neuron 56, 422-437. doi: 10.1016/j.neuron.2007.10.001.
19. Chao, H. T., and Zoghbi, H. Y. (2012). MeCP2: only 100% will do. Nat. Neurosci. 15, 176-177. doi: 10.1038/nn.3027.
20. Christopherson, K. S., Ullian, E. M., Stokes, C. C. A., Mullowney, C. E., Hell, J. W., Agah, A., et al. (2005). Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120, 421-433. doi: 10.1016/j.cell.2004.12.020.
21. Chung, W., Choi, S. Y., Lee, E., Park, H., Kang, J., Choi, Y., et al. (2015). Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression. Nat. Neurosci. 18, 435-443. doi: 10.1038/nn.3927.
22. Chung, W. S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., et al. (2013). Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504, 394-400. doi: 10.1038/nature12776.
23. Clarke, L. E., and Barres, B. A. (2013). Emerging roles of astrocytes in neural circuit development. Nat. Rev. Neurosci. 14, 311-321. doi: 10.1038/nrn3484.
24. Dammann, O., and Leviton, A. (2004). Inflammatory brain damage in preterm newborns - dry numbers, wet lab, and causal inferences. Early Hum. Dev. 79, 1-15. doi: 10.1016/j.earlhumdev.2004.04.009.
25. Derecki, N. C., Cronk, J. C., Lu, Z. J., Xu, E., Abbott, S. B. G., Guyenet, P. G., et al. (2012). Wild-type microglia arrest pathology in a mouse model of Rett syndrome.Nature 484, 105-109. doi: 10.1038/nature10907.
26. Edmonson, C., Ziats, M. N., and Rennert, O. M. (2014). Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum. Mol. Autism 5:9. doi: 10.1186/2040-2392-5-3.
27. Eroglu, C. (2009). The role of astrocyte-secreted matricellular proteins in central nervous system development and function. J. Cell Commun. Signal. 3, 167-176. doi: 10.1007/s12079-009-0078-y.
28. Estes, M. L., and McAllister, A. K. (2015). Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat. Rev. Neurosci. 16, 469-486. doi: 10.1038/nrn3978.
29. Etherton, M., Foldy, C., Sharma, M., Tabuchi, K., Liu, X. R., Shamloo, M., et al. (2011a). Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc. Natl. Acad. Sci. U.S.A. 108, 13764-13769. doi: 10.1073/pnas.1111093108.
30. Etherton, M. R., Tabuchi, K., Sharma, M., Ko, J., and Sudhof, T. C. (2011b). An autism-associated point mutation in the neuroligin cytoplasmic tail selectively impairs AMPA receptor-mediated synaptic transmission in hippocampus. Embo J. 30, 2908-2919. doi: 10.1038/emboj.2011.182.
31. Fatemi, S. H., Folsom, T. D., Reutiman, T. J., and Lee, S. (2008). Expression of astrocytic markers aquaporin 4 and connexin 43 is altered in brains of subjects with autism. Synapse 62, 501-507. doi: 10.1002/syn.20519.
32. Fiacco, T. A., and McCarthy, K. D. (2006). Astrocyte calcium elevations: properties, propagation, and effects on brain signaling. Glia 54, 676-690. doi: 10.1002/glia.20396.
33. Geschwind, D. H. (2009). Advances in Autism. In: Annual Review of Medicine. Palo Alto, CA: Annual Reviews, 367-380.
34. Gowing, G., Philips, T., Van Wijmeersch, B., Audet, J. N., Dewil, M., Van Den Bosch, L., et al. (2008). Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase.J. Neurosci. 28, 10234-10244. doi: 10.1523/JNEUROSCI.3494-08.2008.
35. Grabrucker, A. M. (2012). Environmental factors in autism. Front. Psychiatry2012:118.
36. Gupta, S., Aggarwal, S., Rashanravan, B., and Lee, T. (1998). Th1- and Th2-like cytokines in CD4(+) and CD8(+) T cells in autism. J. Neuroimmunol. 85, 106-109. doi: 10.1016/S0165-5728(98)00021-6.
37. Gupta, S., Ellis, S. E., Ashar, F. N., Moes, A., Bader, J. S., Zhan, J. N., et al. (2014). Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat. Commun. 5:5748. doi: 10.1038/ncomms6748.
38. Habbas, S., Santello, M., Becker, D., Stubbe, H., Zappia, G., Liaudet, N., et al. (2015). Neuroinflammatory TNF alpha impairs memory via astrocyte signaling. Cell 163, 1730-1741. doi: 10.1016/j.cell.2015.11.023.
39. Hagberg, H., Mallard, C., Ferriero, D. M., Vannucci, S. J., Levison, S. W., Vexler, Z. S., et al. (2015). The role of inflammation in perinatal brain injury. Nat. Rev. Neurol. 11, 192-208. doi: 10.1038/nrneurol.2015.13.
40. Halassa, M. M., Fellin, T., Takano, H., Dong, J. H., and Haydon, P. G. (2007). Synaptic islands defined by the territory of a single astrocyte. J. Neurosci. 27, 6473-6477. doi: 10.1523/JNEUROSCI.1419-07.2007.
41. Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., et al. (2011). Genetic heritability and shared environmental factors among twin Pairs with autism. Arch. Genet. Psychiatry 68, 1095-1102. doi: 10.1001/archgenpsychiatry.2011.76.
42. Hanisch, U. K., and Kettenmann, H. (2007). Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387-1394. doi: 10.1038/nn1997.
43. Harrison, J. K., Jiang, Y., Chen, S. Z., Xia, Y. Y., Maciejewski, D., McNamara, R. K., et al. (1998). Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc. Natl. Acad. Sci. U.S.A. 95, 10896-10901. doi: 10.1073/pnas.95.18.10896.
44. Jyonouchi, H., Sun, S. N., and Le, H. (2001). Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J. Neuroimmunol. 120, 170-179. doi: 10.1016/S0165-5728(01)00421-0.
45. Keil, A., Daniels, J. L., Forssen, U., Hultman, C., Cnattingius, S., Soderberg, K. C., et al. (2010). Parental autoimmune diseases associated with autism spectrum disorders in offspring. Epidemiology 21, 805-808. doi: 10.1097/EDE.0b013e3181f26e3f.
46. Kelleher, R. J., and Bear, M. F. (2008). The autistic neuron: troubled translation? Cell135, 401-406. doi: 10.1016/j.cell.2008.10.017.
47. Kettenmann, H. (2011). MICROGLIA. Glia 59, S2-S3.
48. Kettenmann, H., Kirchhoff, F., and Verkhratsky, A. (2013). Microglia: new roles for the synaptic stripper. Neuron 77, 10-18. doi: 10.1016/j.neuron.2012.12.023.
49. Kim, S. H., and Lord, C. (2012). New autism diagnostic interview-revised algorithms for toddlers and young preschoolers from 12 to 47 months of age. J. Autism Dev. Disord. 42, 82-93. doi: 10.1007/s10803-011-1213-1.
50. Knuesel, I., Chicha, L., Britschgi, M., Schobel, S. A., Bodmer, M., Hellings, J. A., et al. (2014). Maternal immune activation and abnormal brain development across CNS disorders. Nat. Rev. Neurol. 10, 643-660. doi: 10.1038/nrneurol.2014.187.
51. Kucukdereli, H., Allen, N. J., Lee, A. T., Feng, A., Ozlu, M. I., Conatser, L. M., et al. (2011). Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins hevin and SPARC. Proc. Natl. Acad. Sci. U.S.A. 108, E440-E449. doi: 10.1073/pnas.1104977108.
52. Li, X. H., Chauhan, A., Sheikh, A. M., Patil, S., Chauhan, V., Li, X. M., et al. (2009). Elevated immune response in the brain of autistic patients. J. Neuroimmunol. 207, 111-116. doi: 10.1016/j.jneuroim.2008.12.002.
53. Lioy, D. T., Garg, S. K., Monaghan, C. E., Raber, J., Foust, K. D., Kaspar, B. K., et al. (2011). A role for glia in the progression of Rett's syndrome. Nature 475, 497-500. doi: 10.1038/nature10214.
54. Maekawa, M., Iwayama, Y., Arai, R., Nakamura, K., Ohnishi, T., Toyota, T., et al. (2010). Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects. J. Hum. Genet.55, 127-130. doi: 10.1038/jhg.2009.133.
55. Maezawa, I., and Jin, L. W. (2010). Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J. Neurosci. 30, 5346-5356. doi: 10.1523/JNEUROSCI.5966-09.2010.
56. Maezawa, I., Swanberg, S., Harvey, D., LaSalle, J. M., and Jin, L. W. (2009). Rett Syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J. Neurosci. 29, 5051-5061. doi: 10.1523/JNEUROSCI.0324-09.2009.
57. Malkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., and Patterson, P. H. (2012). Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav. Immun. 26, 607-616. doi: 10.1016/j.bbi.2012.01.011.
58. McGann, J. C., Lioy, D. T., and Mandel, G. (2012). Astrocytes conspire with neurons during progression of neurological disease. Curr. Opin. Neurobiol. 22, 850-858. doi: 10.1016/j.conb.2012.03.009.
59. Meyer, K. A., Ingersoll, B., and Hambrick, D. Z. (2011). Factors influencing adjustment in siblings of children with autism spectrum disorders. Res. Autism Spect. Disord. 5, 1413-1420. doi: 10.1016/j.rasd.2011.01.027.
60. Ming, X., Johnson, W. G., Stenroos, E. S., Mars, A., Lambert, G. H., and Buyske, S. (2010). Genetic variant of glutathione peroxidase 1 in autism. Brain Dev. 32, 105-109. doi: 10.1016/j.braindev.2008.12.017.
61. Missault, S., Van den Eynde, K., Berghe, W. V., Fransen, E., Weeren, A., Timmermans, J. P., et al. (2014). The risk for behavioural deficits is determined by the maternal immune response to prenatal immune challenge in a neurodevelopmental model.Brain Behav. Immun. 42, 138-146. doi: 10.1016/j.bbi.2014.06.013.
62. Molina-Holgado, F., Toulmond, S., and Rothwell, N. J. (2000). Involvement of interleukin-1 in glial responses to lipopolysaccharide: endogenous versus exogenous interleukin-1 actions. J. Neuroimmunol. 111, 1-9. doi: 10.1016/S0165-5728(00)00344-1.
63. Molofsky, A. V., Krenick, R., Ullian, E., Tsai, H. H., Deneen, B., Richardson, W. D., et al. (2012). Astrocytes and disease: a neurodevelopmental perspective. Genes Dev. 26, 891-907. doi: 10.1101/gad.188326.112.
64. Morgan, J. T., Chana, G., Abramson, I., Semendeferi, K., Courchesne, E., and Everall, I. P. (2012). Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism. Brain Res. 1456, 72-81. doi: 10.1016/j.brainres.2012.03.036.
65. Moynagh, P. N., Williams, D. C., and Oneill, L. A. J. (1993). Interleukin-1 activates transcription factor nf-kappa-b in glial-cells. Biochem. J. 294, 343-347. doi: 10.1042/bj2940343.
66. Murdoch, J. D., and State, M. W. (2013). Recent developments in the genetics of autism spectrum disorders. Curr. Opin. Genet. Dev. 23, 310-315. doi: 10.1016/j.gde.2013.02.003.
67. Nakamura, H., and O'Leary, D. D. M. (1989). Inaccuracies in initial growth and arborization of chick retinotectal axons followed by course corrections and axon remodeling to develop topographic order. J. Neurosci. 9, 3776-3795.
68. Nimmerjahn, A., Kirchhoff, F., and Helmchen, F. (2005). Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314-1318. doi: 10.1126/science.1110647.
69. O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., et al. (2011). Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat. Genet. 43, 585-589. doi: 10.1038/ng.835.
70. Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., et al. (2011). Synaptic pruning by microglia is necessary for normal brain development.Science 333, 1456-1458. doi: 10.1126/science.1202529.
71. Parikshak, N. N., Luo, R., Zhang, A., Won, H., Lowe, J. K., Chandran, V., et al. (2013). Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell 155, 1008-1021. doi: 10.1016/j.cell.2013.10.031.
72. Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., et al. (2013). Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596-1609. doi: 10.1016/j.cell.2013.11.030.
73. Peca, J., and Feng, G. P. (2012). Cellular and synaptic network defects in autism. Curr. Opin. Neurobiol. 22, 866-872. doi: 10.1016/j.conb.2012.02.015.
74. Perez-Garcia, C. G., and O'Leary, D. D. M. (2016). Formation of the cortical subventricular zone requires MDGA1-mediated aggregation of basal progenitors. Cell Rep. doi: 10.1016/j.celrep.2015.12.066 [Epub ahead of print].
75. Pessah, I. N., and Lein, P. J. (2008). "Evidence for environmental susceptibility in autism what we need to know about gene x environment interactions," in Autism: Current Theories and Evidence, ed. A. W. Zimmerman (Totowa, NJ: Humana Press Inc.), 409-428.
76. Petrelli, F., and Bezzi, P. (2016). Novel insights into gliotransmitters. Curr. Opin. Pharmacol. 26, 138-145. doi: 10.1016/j.coph.2015.11.010.
77. Pettem, K. L., Yokomaku, D., Takahashi, H., Ge, Y., and Craig, A. M. (2013). Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development. J. Cell Biol. 200, 321-336. doi: 10.1083/jcb.201206028.
78. Pfrieger, F. W., and Barres, B. A. (1997). Synaptic efficacy enhanced by glia cells in vitro. Science 277, 1684-1687. doi: 10.1126/science.277.5332.1684.
79. Ponzio, N. M., Servatius, R., Beck, K., Marzouk, A., and Kreider, T. (2007). Cytokine levels during pregnancy influence immunological profiles and neurobehavioral patterns of the offspring. Ann. N. Y. Acad. Sci. 1107, 118-128.
80. Purcell, A. E., Jeon, O. H., Zimmerman, A. W., and Pevsner, J. (2001). Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology57, 1618-1628. doi: 10.1212/WNL.57.9.1618.
81. Quaak, I., Brouns, M. R., and Van de Bor, M. (2013). The dynamics of autism spectrum disorders: how neurotoxic compounds and neurotransmitters interact. Int. J. Environ. Res. Public Health 10, 3384-3408. doi: 10.3390/ijerph10083384.
82. Ronesi, J. A., Collins, K. A., Hays, S. A., Tsai, N. P., Guo, W. R., Birnbaum, S. G., et al. (2012). Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat. Neurosci. 15, 431-440. doi: 10.1038/nn.3033.
83. Rosenberg, R. E., Daniels, A. M., Law, J. K., Law, P. A., and Kaufmann, W. E. (2009). Trends in autism spectrum disorder diagnoses: 1994-2007. J. Autism Dev. Disord. 39, 1099-1111. doi: 10.1007/s10803-009-0723-6.
84. Rossi, D. (2015). Astrocyte physiopathology: at the crossroads of intercellular networking, inflammation and cell death. Prog. Neurobiol. 130, 86-120. doi: 10.1016/j.pneurobio.2015.04.003.
85. Sahlender, D. A., Savtchouk, I., and Volterra, A. (2014). What do we know about gliotransmitter release from astrocytes? Philos. Trans. R. Soc. B Biol. Sci.369:20130592. doi: 10.1098/rstb.2013.0592.
86. Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., et al. (2012). De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485, 237-241. doi: 10.1038/nature10945.
87. Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Larsson, H., Hultman, C. M., and Reichenberg, A. (2014). The familial risk of autism. JAMA 311, 1770-1777. doi: 10.1001/jama.2014.4144.
88. Santello, M., Bezzi, P., and Volterra, A. (2011). TNF alpha controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron 69, 988-1001. doi: 10.1016/j.neuron.2011.02.003.
89. Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., et al. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691-705. doi: 10.1016/j.neuron.2012.03.026.
90. Serhan, C. N., and Savill, J. (2005). Resolution of inflammation: the beginning programs the end. Nat. Immunol. 6, 1191-1197. doi: 10.1038/ni1276.
91. Smith, S. E. P., Li, J., Garbett, K., Mirnics, K., and Patterson, P. H. (2007). Maternal immune activation alters fetal brain development through interleukin-6. J. Neurosci.27, 10695-10702. doi: 10.1523/JNEUROSCI.2178-07.2007.
92. Sofroniew, M. V. (2015). Astrocyte barriers to neurotoxic inflammation. Nat. Rev. Neurosci. 16, 249-263. doi: 10.1038/nrn3898.
93. Stanfield, B. B., Oleary, D. D. M., and Fricks, C. (1982). Selective collateral elimination in early postnatal-development restricts cortical distribution of rat pyramidal tract neurons. Nature 298, 371-373. doi: 10.1038/298371a0.
94. State, M. W., and Levitt, P. (2011). The conundrums of understanding genetic risks for autism spectrum disorders. Nat. Neurosci. 14, 1499-1506. doi: 10.1038/nn.2924.
95. Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G., et al. (1989). A twin study of autism in denmark, finland, iceland, norway and sweden.J. Child Psychol. Psychiatry. 30, 405-416. doi: 10.1111/j.1469-7610.1989.tb00254.x.
96. Stellwagen, D., and Malenka, R. C. (2006). Synaptic scaling mediated by glial TNF-alpha. Nature 440, 1054-1059. doi: 10.1038/nature04671.
97. Steven, M. C., Kiehl, K. A., Pearlson, G. D., and Calhoun, V. D. (2007). Functional neural networks underlying response inhibition in adolescents and adults. Behav. Brain Res. 181, 12-22. doi: 10.1016/j.bbr.2007.03.023.
98. Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., et al. (2007). The classical complement cascade mediates CNS synapse elimination.Cell 131, 1164-1178. doi: 10.1016/j.cell.2007.10.036.
99. Suzuki, K., Sugihara, G., Ouchi, Y., Nakamura, K., Futatsubashi, M., Takebayashi, K., et al. (2013). Microglial activation in young adults with autism spectrum disorder.JAMA Psychiatry 70, 49-58. doi: 10.1001/jamapsychiatry.2013.272.
100. Tetreault, N. A., Hakeem, A. Y., Jiang, S., Williams, B. A., Allman, E., Wold, B. J., et al. (2012). Microglia in the cerebral cortex in autism. J. Autism Dev. Disord. 42, 2569-2584. doi: 10.1007/s10803-012-1513-0.
101. Toma, C., Hervas, A., Torrico, B., Balmana, N., Salgado, M., Maristany, M., et al. (2013). Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2. Psychiatr. Genet. 23, 82-85. doi: 10.1097/YPG.0b013e32835d6fc6.
102. Tremblay, M. E., Lowery, R. L., and Majewska, A. K. (2010). Microglial interactions with synapses are modulated by visual experience. PLoS Biol. 8:e1000527. doi: 10.1371/journal.pbio.1000527.
103. Uhlmann, E. J., Wong, M., Baldwin, R. L., Bajenaru, M. L., Onda, H., Kwiatkowski, D. J., et al. (2002). Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann. Neurol. 52, 285-296. doi: 10.1002/ana.10283.
104. Ullian, E. M., Sapperstein, S. K., Christopherson, K. S., and Barres, B. A. (2001). Control of synapse number by glia. Science 291, 657-661. doi: 10.1126/science.291.5504.657.
105. van Bokhoven, H. (2011). Genetic and Epigenetic Networks in Intellectual Disabilities. In: Annual Review Genetics, Vol. 45. Palo Alto, CA: Annual Reviews, 81-104.
106. Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., and Pardo, C. A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol. 57, 67-81. doi: 10.1002/ana.20315.
107. Voineagu, I., Wang, X. C., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., et al. (2011). Transcriptomic analysis of autistic brain reveals convergent molecular pathology.Nature 474, 380-384. doi: 10.1038/nature10110.
108. Watkins, L. R., Milligan, E. D., and Maier, S. F. (2001). Glial activation: a driving force for pathological pain. Trends Neurosci. 24, 450-455. doi: 10.1016/S0166-2236(00)01854-3.
109. Wei, H. G., Zou, H., Sheikh, A. M., Malik, M., Dobkin, C., Brown, W. T., et al. (2011). IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J. Neuroinflamm. 8:52. doi: 10.1186/1742-2094-8-52.
110. Willsey, A. J., Sanders, S. J., Li, M. F., Dong, S., Tebbenkamp, A. T., Muhle, R. A., et al. (2013). Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell 155, 997-1007. doi: 10.1016/j.cell.2013.10.020.
111. Wu, Y. W., Dissing-Olesen, L., MacVicar, B. A., and Stevens, B. (2015). Microglia: dynamic mediators of synapse development and plasticity. Trends Immunol. 36, 605-613. doi: 10.1016/j.it.2015.08.008.
112. Yasui, D. H., Xu, H. C., Dunaway, K. W., LaSalle, J. M., Jin, L. W., and Maezawa, I. (2013). MeCP2 modulates gene expression pathways in astrocytes. Mol. Autism 4:3. doi: 10.1186/2040-2392-4-3.
113. Yuskaitis, C. J., Beurel, E., and Jope, R. S. (2010). Evidence of reactive astrocytes but not peripheral immune system activation in a mouse model of Fragile X syndrome.Biochim. Biophys. Acta Mol. Basis Dis. 1802, 1006-1012. doi: 10.1016/j.bbadis.2010.06.015.
114. Zhan, Y., Paolicelli, R. C., Sforazzini, F., Weinhard, L., Bolasco, G., Pagani, F., et al. (2014). Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci. 17, 400-406. doi: 10.1038/nn.3641.
115. Zhang, P. S., Miller, B. S., Rosenzweig, S. A., and Bhat, N. R. (1996). Activation of c-Jun N-terminal kinase stress-activated protein kinase in primary glial cultures. J. Neurosci. Res. 46, 114-121. doi: 10.1002/(SICI)1097-4547(19961001)46:1<114::AID-JNR14>3.0.CO;2-5.