Gene expression analysis in Fmr1KO mice identifies an immunological signature in brain tissue and mGluR5-related signaling in primary neuronal cultures

Molecular Autism

Volumn 6, Issue 1, 2015, Pages

  Prilutsky, Daria ^a   Kho, Alvin T ^b   Palmer, Nathan P ^a   Bhakar, Asha L ^c   Smedemark Margulies, Niklas ^a   Kong, Sek Won ^a,b   Margulies, David M ^a   Bear, Mark F ^c   Kohane, Isaac S ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Brain; Fragile X syndrome; Gene expression; Murine model; Neuronal cultures

Indexed keywords

FRAGILE X MENTAL RETARDATION PROTEIN; METABOTROPIC RECEPTOR 5; TRANSCRIPTOME;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN; BRAIN CORTEX; BRAIN DEVELOPMENT; CELL ACTIVITY; CONTROLLED STUDY; DEVELOPMENTAL STAGE; DOWN REGULATION; EMBRYO; FMR1 GENE; FRAGILE X SYNDROME; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE FUNCTION; GENETIC ASSOCIATION; GENOTYPE; HIPPOCAMPUS; IMMUNOLOGY; IN VITRO STUDY; KNOCKOUT GENE; KNOCKOUT MOUSE; MOUSE; NERVE CELL CULTURE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; UPREGULATION;

EID: 84955412628     PISSN: None     EISSN: 20402392     Source Type: Journal    
DOI: 10.1186/s13229-015-0061-9     Document Type: Article

References (47)

1. Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci. 2004;27(7):370-7. doi: 10.1016/j.tins.2004.04.009.
2. Bhakar AL, Dolen G, Bear MF. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci. 2012;35:417-43. doi: 10.1146/annurev-neuro-060909-153138.
3. Koukoui SD, Chaudhuri A. Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome. Brain Res Rev. 2007;53(1):27-38. doi: 10.1016/j.brainresrev.2006.06.001.
4. Huber KM, Gallagher SM, Warren ST, Bear MF. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A. 2002;99(11):7746-50. doi: 10.1073/pnas.122205699.
5. Dolen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, et al. Correction of fragile X syndrome in mice. Neuron. 2007;56(6):955-62. doi: 10.1016/j.neuron.2007.12.001.
6. Dolen G, Carpenter RL, Ocain TD, Bear MF. Mechanism-based approaches to treating fragile X. Pharmacol Ther. 2010;127(1):78-93. doi: 10.1016/j.pharmthera.2010.02.008.
7. Krueger DD, Bear MF. Toward fulfilling the promise of molecular medicine in fragile X syndrome. Annu Rev Med. 2011;62:411-29. doi: 10.1146/annurev-med-061109-134644.
8. Antar LN, Li C, Zhang H, Carroll RC, Bassell GJ. Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses. Mol Cell Neurosci. 2006;32(1-2):37-48. doi: 10.1016/j.mcn.2006.02.001.
9. Galvez R, Greenough WT. Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome. Am J Med Genet A. 2005;135(2):155-60. doi: 10.1002/ajmg.a.30709.
10. Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet. 2001;98(2):161-7.
11. Nimchinsky EA, Oberlander AM, Svoboda K. Abnormal development of dendritic spines in FMR1 knock-out mice. J Neurosci. 2001;21(14):5139-46.
12. Pfeiffer BE, Huber KM. Fragile X mental retardation protein induces synapse loss through acute postsynaptic translational regulation. J Neurosci. 2007;27(12):3120-30. doi: 10.1523/JNEUROSCI.0054-07.2007.
13. Nakamoto M, Nalavadi V, Epstein MP, Narayanan U, Bassell GJ, Warren ST. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci U S A. 2007;104(39):15537-42. doi: 10.1073/pnas.0707484104.
14. Schmid PR, Palmer NP, Kohane IS, Berger B. Making sense out of massive data by going beyond differential expression. Proc Natl Acad Sci U S A. 2012;109(15):5594-9. doi: 10.1073/pnas.1118792109.
15. Butte AJ, Kohane IS. Creation and implications of a phenome-genome network. Nat Biotechnol. 2006;24(1):55-62. doi: 10.1038/nbt1150.
16. Kho AT, Zhao Q, Cai Z, Butte AJ, Kim JY, Pomeroy SL, et al. Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers. Genes Dev. 2004;18(6):629-40. doi: 10.1101/gad.1182504.
17. Naxerova K, Bult CJ, Peaston A, Fancher K, Knowles BB, Kasif S, et al. Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers. Genome Biol. 2008;9(7):R108. doi: 10.1186/gb-2008-9-7-r108.
18. Bhakar AL, Tannis LL, Zeindler C, Russo MP, Jobin C, Park DS, et al. Constitutive nuclear factor-kappa B activity is required for central neuron survival. J Neurosci. 2002;22(19):8466-75.
19. Melen E, Kho AT, Sharma S, Gaedigk R, Leeder JS, Mariani TJ, et al. Expression analysis of asthma candidate genes during human and murine lung development. Respir Res. 2011;12:86. doi: 10.1186/1465-9921-12-86.
20. Alter O, Brown PO, Botstein D. Singular value decomposition for genome-wide expression data processing and modeling. Proc Natl Acad Sci U S A. 2000;97(18):10101-6.
21. Misra J, Schmitt W, Hwang D, Hsiao LL, Gullans S, Stephanopoulos G. Interactive exploration of microarray gene expression patterns in a reduced dimensional space. Genome Res. 2002;12(7):1112-20. doi: 10.1101/gr.225302.
22. Mouse Gene Informatics. http://www.informatics.jax.org/searches/Phat.cgi?id=MP:0005386. Accessed May, 2014.
23. Simons Foundation Autism Research Initiative. https://gene.sfari.org. Accessed on May, 2015.
24. Ascano Jr M, Mukherjee N, Bandaru P, Miller JB, Nusbaum JD, Corcoran DL, et al. FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature. 2012;492(7429):382-6. doi: 10.1038/nature11737.
25. Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011;478(7370):483-9. doi: 10.1038/nature10523.
26. Huguet G, Ey E, Bourgeron T. The genetic landscapes of autism spectrum disorders. Annu Rev Genomics Hum Genet. 2013;14:191-213. doi: 10.1146/annurev-genom-091212-153431.
27. Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature. 2011;474(7351):380-4. doi: 10.1038/nature10110.
28. Gupta S, Ellis SE, Ashar FN, Moes A, Bader JS, Zhan J, et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun. 2014;5:5748. doi: 10.1038/ncomms6748.
29. Kong SW, Sahin M, Collins CD, Wertz MH, Campbell MG, Leech JD, et al. Divergent dysregulation of gene expression in murine models of fragile X syndrome and tuberous sclerosis. Mol Autism. 2014;5(1):16. doi: 10.1186/2040-2392-5-16.
30. Jung JY, Kohane IS, Wall DP. Identification of autoimmune gene signatures in autism. Transl Psychiatry. 2011;1:e63. doi: 10.1038/tp.2011.62.
31. Kong SW, Collins CD, Shimizu-Motohashi Y, Holm IA, Campbell MG, Lee IH, et al. Characteristics and predictive value of blood transcriptome signature in males with autism spectrum disorders. PLoS One. 2012;7(12):e49475. doi: 10.1371/journal.pone.0049475.
32. Garbett K, Ebert PJ, Mitchell A, Lintas C, Manzi B, Mirnics K, et al. Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiol Dis. 2008;30(3):303-11. doi: 10.1016/j.nbd.2008.01.012.
33. Korvatska E, Van de Water J, Anders TF, Gershwin ME. Genetic and immunologic considerations in autism. Neurobiol Dis. 2002;9(2):107-25. doi: 10.1006/nbdi.2002.0479.
34. Cohly HH, Panja A. Immunological findings in autism. Int Rev Neurobiol. 2005;71:317-41.
35. Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, et al. Elevated immune response in the brain of autistic patients. J Neuroimmunol. 2009;207(1-2):111-6. doi: 10.1016/j.jneuroim.2008.12.002.
36. Garay PA, McAllister AK. Novel roles for immune molecules in neural development: implications for neurodevelopmental disorders. Front Synaptic Neurosci. 2010;2:136. doi: 10.3389/fnsyn.2010.00136.
37. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10(11):1387-94. doi: 10.1038/nn1997.
38. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67-81. doi: 10.1002/ana.20315.
39. Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Futatsubashi M, Takebayashi K, et al. Microglial activation in young adults with autism spectrum disorder. JAMA Psychiatry. 2013;70(1):49-58. doi: 10.1001/jamapsychiatry.2013.272.
40. Morgan JT, Chana G, Pardo CA, Achim C, Semendeferi K, Buckwalter J, et al. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry. 2010;68(4):368-76. doi: 10.1016/j.biopsych.2010.05.024.
41. Yuskaitis CJ, Beurel E, Jope RS. Evidence of reactive astrocytes but not peripheral immune system activation in a mouse model of Fragile X syndrome. Biochim Biophys Acta. 2010;1802(11):1006-12. doi: 10.1016/j.bbadis.2010.06.015.
42. Kim KH, Son SM, Mook-Jung I. Contributions of microglia to structural synaptic plasticity. J Exp Neurosci. 2013;7:85-91. doi: 10.4137/JEN.S11269.
43. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. Synaptic pruning by microglia is necessary for normal brain development. Science. 2011;333(6048):1456-8. doi: 10.1126/science.1202529.
44. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74(4):691-705. doi: 10.1016/j.neuron.2012.03.026.
45. Schafer DP, Stevens B. Synapse elimination during development and disease: immune molecules take centre stage. Biochem Soc Trans. 2010;38(2):476-81. doi: 10.1042/BST0380476.
46. Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol. 2006;80(1):1-15. doi: 10.1189/jlb.1205707.
47. Pardo CA, Vargas DL, Zimmerman AW. Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry. 2005;17(6):485-95. doi: 10.1080/02646830500381930.