Rett syndrome: Genes, synapses, circuits, and therapeutics

Frontiers in Psychiatry

Volumn 3, Issue MAY, 2012, Pages

  Banerjee, Abhishek ^a   Castro, Jorge ^a   Sur, Mriganka ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Development; Plasticity; RTT; Synapse; Visual cortex

Indexed keywords

1,4 BENZODIOXAN 6 CARBOXYLIC ACID PIPERIDIDE; BRAIN DERIVED NEUROTROPHIC FACTOR; DESIPRAMINE; METHYL CPG BINDING PROTEIN 2; SOMATOMEDIN C;

DIET SUPPLEMENTATION; EXCITATORY POSTSYNAPTIC POTENTIAL; EXPERIMENTAL MODEL; FRAGILE X SYNDROME; GENE; GENE EXPRESSION; GENE MUTATION; GENETIC MANIPULATION; GLIA CELL; HUMAN; INHIBITORY POSTSYNAPTIC POTENTIAL; INTRACELLULAR SIGNALING; METHYL CPG BINDING PROTEIN 2 GENE; MOLECULAR PATHOLOGY; NERVE CELL PLASTICITY; NONHUMAN; PROTEIN DEPLETION; PROTEIN FUNCTION; RETT SYNDROME; REVIEW; SYNAPTIC TRANSMISSION; TUBEROUS SCLEROSIS;

EID: 84866725323     PISSN: None     EISSN: 16640640     Source Type: Journal    
DOI: 10.3389/fpsyt.2012.00034     Document Type: Review

References (117)

1. Abuhatzira, L., Makedonski, K., Kaufman, Y., Razin, A., and Shemer, R. (2007). MeCP2 deficiency in the brain decreases BDNF levels by REST/CoREST-mediated repression and increases TRKB production. Epigenetics 2, 214-222.
2. Adkins, N. L., and Georgel, P. T. (2011). MeCP2: structure and function. Biochem. Cell Biol. 89,1-11.
3. Adler, D. A., Quaderi, N. A., Brown, S. D., Chapman, V. M., Moore, J., Tate, P., and Disteche, C. M. (1995). The X-linked methylated DNA binding protein, Mecp2, is subject to X inactivation in the mouse. Mamm. Genome 6,491-492.
4. Amir, R. E., Van Den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., and Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23,185-188.
5. Armstrong, D. D. (2005). Neuropathology of Rett syndrome. J. Child Neurol. 20, 747-753.
6. Asaka, Y., Jugloff, D. G., Zhang, L., Eubanks, J. H., and Fitzsimonds, R. M. (2006). Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol. Dis. 21, 217-227.
7. Auerbach, B. D., Osterweil, E. K., and Bear, M. F. (2011). Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480, 63-68.
8. Ballas, N., Lioy, D. T., Grunseich, C., and Mandel, G. (2009). Non-cellautonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat. Neurosci. 12, 311-317.
9. Belichenko, P. V., Wright, E. E., Belichenko, N. P., Masliah, E., Li, H. H., Mobley, W C, and Francke, U. (2009). Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of Rett syndrome: evidence for disruption of neuronal networks. J. Comp. Neurol. 514,240-258.
10. Ben-Ari, Y., and Spitzer, N. C. (2010). Phenotypic checkpoints regulate neuronal development. Trends Neurosci. 33,485-492.
11. Beretta, L., Gingras, A. C., Svitkin, Y. V., Hall, M. N., and Sonenberg, N. (1996). Rapamycin blocks the phos-phorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBOJ. 15, 658-664.
12. Blue, M. E., Kaufmann, W. E., Bressler, J., Eyring, C., O'Driscoll, C., Naidu, S., and Johnston, M. V. (2011). Temporal and regional alterations in NMDA receptor expression in Mecp2-null mice. Anat. Rec. (Hoboken) 294,1624-1634.
13. Calfa, G., Hablitz, J. J., and Pozzo-Miller, L. (2011a). Network hyper-excitability in hippocampal slices from Mecp2 mutant mice revealed by voltage-sensitive dye imaging. J. Neurophysiol. 105, 1768-1784.
14. Calfa, G., Percy, A. K., and Pozzo-Miller, L. (2011b). Experimental models of Rett syndrome based on Mecp2 dysfunction. Exp. Biol. Med. (Maywood) 236,3-19.
15. Castro, J., Kwok, S., Garcia, R., and Sur, M. (2011). Effects of recombinant human IGF1 treatment in a mouse model of Rett syndrome. Paper Presentation in Society for Neuroscience. Poster number cited 59.17/DD26.
16. Chahrour, M., and Zoghbi, H. Y (2007). The story of Rett syndrome: from clinic to neurobiology. Neuron 56, 422-437.
17. Chang, Q., Khare, G., Dani, V., Nelson, S., and Jaenisch, R. (2006). The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49, 341-348.
18. Chao, H. T., Chen, H., Samaco, R. C., Xue, M., Chahrour, M., Yoo, J., Neul, J. L., Gong, S., Lu, H. C., Heintz, N., Ekker, M., Rubenstein, J. L., Noebels, J. L., Rosenmund, C., and Zoghbi, H. Y (2010). Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468, 263-269.
19. Chao, H. T., and Zoghbi, H. Y. (2012). MeCP2: only 100% will do. Nat. Neurosci. 15, 176-177.
20. Chao, H. T., Zoghbi, H. Y., and Rosenmund, C. (2007). MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron 56, 58-65.
21. Chen, R. Z., Akbarian, S., Tudor, M., and Jaenisch, R. (2001). Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat. Genet. 27, 327-331.
22. ohen, S., Gabel, H. W., Hemberg, M., Hutchinson, A. N., Sadacca, L. A., Ebert, D. H., Harmin, D. A., Greenberg, R. S., Verdine, V. K., Zhou, Z., Wetsel, W. C., West, A. E., and Greenberg, M. E. (2011). Genome-Wide activity-dependent MeCP2 phos-phorylation regulates nervous system development and function. Neuron 72, 72-85.
23. Collins, A. L., Levenson, J. M., Vilaythong, A. P., Richman, R., Armstrong, D. L., Noebels, J. L., David Sweatt, J., and Zoghbi, H. Y (2004). Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum. Mol. Genet. 13,2679-2689.
24. Cuesto, G., Enriquez-Barreto, L., Carames, C., Cantarero, M., Gasull, X., Sandi, C., Ferrus, A., Acebes, A., and Morales, M. (2011). Phosphoinositide-3-kinase activation controls synaptogenesis and spinogenesis in hippocampal neurons.J. Neurosci. 31,2721-2733.
25. Dani, V. S., Chang, Q., Maffei, A., Turrigiano, G. G., Jaenisch, R., and Nelson, S. B. (2005). Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. Proc. Natl. Acad. Sci. U.S.A. 102,12560-12565.
26. Dani, V. S., and Nelson, S. B. (2009). Intact long-term poten-tiation but reduced connectivity between neocortical layer 5 pyramidal neurons in a mouse model of Rett syndrome. J. Neurosci. 29, 11263-11270.
27. Dastidar, S. G., Bardai, F. H., Ma, C., Price, V., Rawat, V., Verma, P., Narayanan, V., and D'Mello, S. R. (2012). Isoform-specific toxicity of Mecp2 in postmitotic neurons: suppression of neurotoxicity by FoxG1. J. Neurosci. 32, 2846-2855.
28. De Filippis, B., Ricceri, L., and Laviola, G. (2010). Early postnatal behavioral changes in the Mecp2-308 truncation mouse model of Rett syndrome. Genes Brain Behav. 9, 213-223.
29. Derecki,N.C.,Cronk,J.C.,Lu,Z.,Xu,E., Abbott, S.B.,Guyenet, P. G., and Kipnis, J. (2012). Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484, 105-109.
30. Derecki, N. C., Privman, E., and Kipnis, J. (2010). Rett syndrome and other autism spectrum disorders-brain diseases of immune malfunction? Mol. Psychiatry 15, 355-363.
31. Dragich, J. M., Kim, Y. H., Arnold, A. P., andSchanen,N.C. (2007). Differential distribution of the MeCP2 splice variants in the postnatal mouse brain.J. Comp. Neurol. 501,526-542.
32. Dufner, A., Andjelkovic, M., Burger-ing, B. M., Hemmings, B. A., and Thomas, G. (1999). Protein kinase B localization and activation differentially affect S6 kinase 1 activity and eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation. Mol. Cell. Biol. 19, 4525-4534.
33. Fukuda, T., Itoh, M., Ichikawa, T., Washiyama, K., and Goto, Y. (2005). Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J. Neuropathol. Exp. Neurol. 64, 537-544.
34. Gallagher, S. M., Daly, C. A., Bear, M. F., and Huber, K. M. (2004). Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1. J. Neurosci. 24,4859-4864.
35. Galvao, T. C., and Thomas, J. O. (2005). Structure-specific binding of MeCP2 to four-way junction DNA through its methyl CpG-binding domain. Nucleic Acids Res. 33, 6603-6609.
36. Gemelli, T., Berton, O., Nelson, E. D., Perrotti, L. I., Jaenisch, R., and Mon-teggia, L. M. (2006). Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biol. Psychiatry 59, 468-476.
37. Giacometti, E., Luikenhuis, S., Beard, C., and Jaenisch, R. (2007). Partialrescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc. Natl. Acad. Sci. U.S.A. 104, 1931-1936.
38. Goffin, D., Allen, M., Zhang, L., Amorim,M.,Wang,I.T. J., Reyes, A.-R. S., Mercado-Berton, A., Ong, C., Cohen, S., Hu, L., Blendy, J. A., Carlson, G. C., Siegel, S. J., Greenberg, M. E., and Zhou, Z. (2012). Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Nat. Neurosci. 15,274-283.
39. Graeber, M. B., and Streit, W. J. (2010). Microglia: biology and pathology. Acta Neuropathol. 119,89-105.
40. Gross, C.,Nakamoto, M.,Yao,X., Chan, C. B., Yim, S. Y., Ye, K., Warren, S. T., and Bassell, G. J. (2010). Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J. Neurosci. 30, 10624-10638.
41. Guy, J., Cheval, H., Selfridge, J., and Bird, A. (2011). The role of MeCP2 in the brain. Annu. Rev. Cell Dev. Biol. 27, 631-652.
42. Guy, J., Gan, J., Selfridge, J., Cobb, S., and Bird, A. (2007). Reversal of neurological defects in a mouse model of Rett syndrome. Science 315, 1143-1147.
43. Guy, J., Hendrich, B., Holmes, M., Martin, J. E., and Bird, A. (2001). A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat. Genet. 27, 322-326.
44. Hagberg, B., Aicardi, J., Dias, K., and Ramos, O. (1983). A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann. Neurol. 14,471-479.
45. Hendrich, B., and Bird, A. (1998). Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol. Cell. Biol. 18, 6538-6547.
46. Hou, L., Antion, M. D., Hu, D., Spencer, C. M., Paylor, R., and Klann, E. (2006). Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 51, 441-454.
47. Hou, L., and Klann, E. (2004). Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J. Neurosci. 24, 6352-6361.
48. Huang, H. S., Allen, J. A., Mabb, A. M., King, I. F., Miriyala, J., Taylor-Blake, B., Sciaky, N., Dutton, J. W.Jr., Lee, H. M., Chen, X., Jin, J., Bridges, A. S.,Zylka, M. J., Roth, B. L., and Philpot, B. D. (2012). Topoiso-merase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481,185-189.
49. Inoki, K., Li, Y., Zhu, T., Wu, J., and Guan, K. L. (2002). TSC2 is phos-phorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4, 648-657.
50. Jaworski, J., Spangler, S., Seeburg, D. P., Hoogenraad, C. C., and Sheng, M. (2005). Control of dendritic arborization by the phosphoi-nositide-3'-kinase-Akt-mammalian target of rapamycin pathway. J. Neurosci.25, 11300-11312.
51. Jugloff, D. G., Vandamme, K., Logan, R., Visanji, N. P., Brotchie, J. M., and Eubanks, J. H. (2008). Targeted delivery of an Mecp2 trans-gene to forebrain neurons improves the behavior of female Mecp2-deficient mice. Hum. Mol. Genet. 17, 1386-1396.
52. Kerr, B., Alvarez-Saavedra, M., Saez, M. A., Saona, A., and Young, J. I. (2008). Defective body-weight regulation, motor control and abnormal social interactions in Mecp2 hypo-morphic mice. Hum. Mol. Genet. 17, 1707-1717.
53. Kerr, B., Silva, P. A., Walz, K., and Young, J. I. (2010). Unconventional tran-scriptional response to environmental enrichment in a mouse model of Rett syndrome. PLoS ONE 5, e 11534. doi:10.1371/journal.pone.0011534
54. Kim, K. Y., Hysolli, E., and Park, I. H. (2011). Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc. Natl. Acad. Sci. U.S.A. 108, 14169-14174.
55. Kishi, N., and Macklis, J. D. (2004). MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol. Cell. Neurosci. 27, 306-321.
56. Kline, D. D., Ogier, M., Kunze, D. L., and Katz, D. M. (2010). Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in Mecp2-null mice. J. Neurosci. 30, 5303-5310.
57. Kriaucionis, S., Paterson, A., Curtis, J., Guy, J., Macleod, N., and Bird, A. (2006). Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. Mol. Cell. Biol. 26, 5033-5042.
58. Kumar, V., Zhang, M. X., Swank, M. W., Kunz, J., and Wu, G. Y (2005). Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR andRas-MAPK signaling pathways. J. Neurosci. 25, 11288-11299.
59. Lee, C. C., Huang, C. C., Wu, M. Y., and Hsu, K. S. (2005). Insulin stimulates postsynaptic density-95 protein translation via the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway. J. Biol. Chem. 280,18543-18550.
60. Lewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F., and Bird, A. (1992). Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69, 905-914.
61. Lin, T. A., Kong, X., Haystead, T. A., Pause, A., Belsham, G., Sonenberg, N., and Lawrence, J. C. Jr. (1994). PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Science 266,653-656.
62. Lioy, D. T., Garg, S. K., Monaghan, C. E., Raber, J., Foust, K. D., Kaspar, B. K., Hirrlinger, P. G., Kirchhoff, F., Bissonnette, J. M., Ballas, N., and Mandel, G. (2011). A role for glia in the progression of Rett's syndrome. Nature 475, 497-500.
63. Lonetti, G., Angelucci, A., Morando, L., Boggio, E. M., Giustetto, M., and Pizzorusso,T. (2010). Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice. Biol. Psychiatry 67, 657-665.
64. Luikenhuis, S., Giacometti, E., Beard, C. F., and Jaenisch, R. (2004). Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc. Natl. Acad. Sci. U.S.A. 101, 6033-6038.
65. Maezawa, I., and Jin, L. W (2010). Rett syndrome microglia damage den-drites and synapses by the elevated release of glutamate. J. Neurosci. 30, 5346-5356.
66. Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., and Cantley, L. C. (2002). Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10, 151-162.
67. Marchetto, M. C., Brennand, K. J., Boyer, L. F., and Gage, F H. (2011). Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Hum. Mol. Genet. 20, R109-R115.
68. Mazroui, R., Huot, M. E., Tremblay, S., Filion, C., Labelle, Y., and Khandjian, E. W. (2002). Trapping of messenger RNA by fragile X mental retardation protein into cytoplasmic granules induces translation repression. Hum. Mol. Genet. 11, 3007-3017.
69. McGill, B. E., Bundle, S. F., Yaylaoglu, M. B., Carson, J. P., Thaller, C., and Zoghbi, H. Y. (2006). Enhanced anxiety and stress-induced corticos-terone release are associated with increased Crh expression in a mouse model of Rett syndrome. Proc. Natl. Acad. Sci. U.S.A. 103, 18267-18272.
70. McGraw, C. M., Samaco, R. C., and Zoghbi, H. Y. (2011). Adult neural function requires MeCP2. Science 333, 186.
71. Medrihan, L., Tantalaki, E., Aramuni, G., Sargsyan, V., Dudanova, I., Missler, M., and Zhang, W. (2008). Early defects of GABAergic synapses in the brain stem of aMeCP2 mouse model of Rett syndrome. J. Neurophysiol. 99,112-121.
72. Mnatzakanian, G. N., Lohi, H., Munteanu, I., Alfred, S. E., Yamada, T., Macleod, P. J., Jones, J. R., Scherer, S. W., Schanen, N. C., Friez, M. J., Vincent, J. B., and Minassian, B. A. (2004). A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat. Genet. 36, 339-341.
73. Moretti, P., Bouwknecht, J. A., Teague, R., Paylor, R., and Zoghbi, H. Y. (2005). Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Hum. Mol. Genet. 14, 205-220.
74. Moretti, P., Levenson, J. M., Battaglia, F., Atkinson, R., Teague, R., Antalffy, B., Armstrong, D.,Arancio,O.,Sweatt, J. D., and Zoghbi, H. Y. (2006). Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J. Neurosci. 26, 319-327.
75. Moy, S. S., Nadler, J. J., Young, N. B., Nonneman, R. J., Grossman, A. W., Murphy, D. L., D'Ercole, A. J., Crawley, J. N., Magnuson, T. R., and Lauder, J. M. (2009). Social approach in genetically engineered mouse lines relevant to autism. Genes Brain Behav. 8, 129-142.
76. Moy, S. S., Nadler, J. J., Young, N. B., Nonneman, R. J., Segall, S. K., Andrade, G. M., Crawley, J. N., and Magnuson, T. R. (2008). Social approach and repetitive behavior in eleven inbred mouse strains. Behav. Brain Res. 191, 118-129.
77. Moy, S. S., Nadler, J. J., Young, N. B., Perez, A., Holloway, L. P., Barbaro, R. P., Barbaro, J. R., Wilson, L. M., Threadgill, D. W., Lauder, J. M., Magnuson, T. R., and Crawley, J. N. (2007). Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav. Brain Res. 176, 4-20.
78. Muotri, A. R., Marchetto, M. C., Coufal, N. G., Oefner, R., Yeo, G., Nakashima, K., and Gage, F. H. (2010). L1 retrotransposition in neurons is modulated by MeCP2. Nature 468, 443-446.
79. Nag, N., and Berger-Sweeney, J. E. (2007). Postnatal dietary choline supplementation alters behavior in a mouse model of Rett syndrome. Neurobiol. Dis. 26, 473-480.
80. Nag, N., Moriuchi, J. M., Peitzman, C. G., Ward, B. C., Kolodny, N. H., and Berger-Sweeney, J. E. (2009). Environmental enrichment alters loco-motor behaviour and ventricular volume in Mecp2 1lox mice. Behav. Brain Res. 196,44-48.
81. Nan, X., Campoy, E J., and Bird, A. (1997). MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 88, 471-481.
82. Nan, X., Meehan, R. R., and Bird, A. (1993). Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res. 21,4886-4892.
83. Nelson, E. D., Kavalali, E. T., and Monteggia, L. M. (2006). MeCP2-dependent transcriptional repression regulates excitatory neurotrans-mission. Curr. Biol. 16,710-716.
84. Nomura, Y. (2005). Early behavior characteristics and sleep disturbance in Rett syndrome. Brain Dev. 27(Suppl. 1),S35-S42.
85. Noutel, J., Hong, Y. K., Leu, B., Kang, E., and Chen, C. (2011). Experience-dependent retinogeniculate synapse remodeling is abnormal in MeCP2-deficient mice. Neuron 70, 35-42.
86. Ogier, M., Wang, H., Hong, E., Wang, Q., Greenberg, M. E., and Katz, D. M. (2007). Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J. Neurosci. 27, 10912-10917.
87. Panayotis, N., Pratte, M., Borges-Correia, A., Ghata, A., Villard, L., and Roux, J. C. (2011). Morphological and functional alterations in the sub-stantia nigra pars compacta of the Mecp2-null mouse. Neurobiol. Dis. 41,385-397.
88. Pratte, M., Panayotis, N., Ghata, A., Villard, L., and Roux, J. C. (2011). Progressive motor and respiratory metabolism deficits in post-weaning Mecp2-null male mice. Behav. Brain Res. 216, 313-320.
89. Qin, M., Kang, J., Burlin, T. V., Jiang, C., and Smith, C. B. (2005). Postado-lescent changes in regional cerebral protein synthesis: an in vivo study inhe FMR1 null mouse. J. Neurosci. 25,5087-5095.
90. Qiu, Z., Sylwestrak, E. L., Lieberman, D. N., Zhang, Y., Liu, X. Y., and Ghosh, A. (2012). The Rett syndrome protein MeCP2 regulates synaptic scaling. J. Neurosci. 32, 989-994.
91. Rett, A. (1966). On aunusual brain atrophy syndrome in hyperammonemia in childhood. Wien. Med. Wochen-schr. 116,723-726.
92. Ricceri, L., De Filippis, B., Fuso, A., and Laviola, G. (2011). Cholinergic hypofunction in MeCP2-308 mice: beneficial neurobehavioural effects of neonatal choline supplementation. Behav. Brain Res. 221, 623-629.
93. Ricciardi, S., Boggio, E. M., Grosso, S., Lonetti, G., Forlani, G., Stefanelli, G., Calcagno, E., Morello, N., Land-sberger, N., Biffo, S., Pizzorusso, T., Giustetto, M., and Broccoli, V (2011). Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model. Hum. Mol. Genet. 20,1182-1196.
94. Roux, J. C., Dura, E., Moncla, A., Mancini, J., and Villard, L. (2007). Treatment with desipramine improves breathing and survival in a mouse model for Rett syndrome. Eur. J. Neurosci. 25,1915-1922.
95. Santos, M., Silva-Fernandes, A., Oliveira, P., Sousa, N., and Maciel, P. (2007). Evidence for abnormal early development in a mouse model of Rett syndrome. Genes Brain Behav. 6, 277-286.
96. Schaevitz, L. R., Moriuchi, J. M., Nag, N., Mellot, T. J., and Berger-Sweeney, J. (2010). Cognitive and social functions and growth factors in a mouse model of Rett syndrome. Physiol. Behav. 100, 255-263.
97. Schmid, D. A., Yang, T., Ogier, M., Adams, I., Mirakhur, Y., Wang, Q., Massa, S. M., Longo, E M., and Katz, D. M. (2012). A TrkB small molecule partial agonist rescues TrkB phos-phorylation deficits and improves respiratory function in a mouse model of Rett syndrome. J. Neurosci. 32,1803-1810.
98. Schule, B., Armstrong, D. D., Vogel, H., Oviedo, A., and Francke, U. (2008). Severe congenital encephalopathy caused by MECP2 null mutations in males: central hypoxia and reduced neuronal dendritic structure. Clin. Genet. 74, 116-126.
99. Shahbazian, M., Young, J., Yuva-Paylor, L., Spencer, C., Antalffy, B., Noebels, J., Armstrong, D., Paylor, R., and Zoghbi, H. (2002a). Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35,243-254.
100. Shahbazian, M. D., Antalffy, B., Armstrong, D. L., and Zoghbi, H. Y. (2002b). Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum. Mol. Genet. 11,115-124.
101. Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., Mcbride, S. M., Klann, E., and Zukin, R. S. (2010). Dysregulation of mTOR signaling in fragile X syndrome. J. Neurosci. 30, 694-702.
102. Stearns, N. A., Schaevitz, L. R., Bowling, H., Nag, N., Berger, U. V., and Berger-Sweeney, J. (2007). Behavioral and anatomical abnormalities in Mecp2 mutant mice: a model for Rett syndrome. Neuroscience 146, 907-921.
103. Steffenburg, U., Hagberg, G., and Hag-berg, B. (2001). Epilepsy in a representative series of Rett syndrome. Acta Paediatr. 90, 34-39.
104. Sutton, M. A., and Schuman, E. M. (2006). Dendritic protein synthesis, synaptic plasticity, and memory. Cell 127,49-58.
105. Talos, D. M., Kwiatkowski, D. J., Cordero, K., Black, P. M., and Jensen, F. E. (2008). Cell-specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers. Ann. Neurol. 63, 454-465.
106. Tavazoie, S. F., Alvarez, V A., Ride-nour, D. A., Kwiatkowski, D. J., and Sabatini, B. L. (2005). Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat. Neurosci. 8, 1727-1734.
107. Trappe, R., Laccone, F., Cobilanschi, J., Meins, M., Huppke, P., Hanefeld, E, and Engel, W. (2001). MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am. J. Hum. Genet. 68, 1093-1101.
108. Tremblay, M. E., Stevens, B., Sierra, A., Wake, H., Bessis, A., and Nimmer-jahn, A. (2011). The role of microglia in the healthy brain. J. Neurosci. 31, 16064-16069.
109. Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., Mccurry, C., Fu, D. D., Flannery, R., Jaenisch, R., and Sur, M. (2009). Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc. Natl. Acad. Sci. U.S.A 106, 2029-2034.
110. Turrigiano, G. G., and Nelson, S. B. (2004). Homeostatic plasticity in the developing nervous system. Nat. Rev. Neurosci. 5, 97-107.
111. Ward, B.C., Kolodny, N.H., Nag, N., and Berger-Sweeney, J. E. (2009). Neuro-chemical changes in a mouse modelof Rett syndrome: changes over time and in response to perinatal choline nutritional supplementation. J. Neu-rochem. 108, 361-371.
112. Williamson, S. L., and Christodoulou, J. (2006). Rett syndrome: new clinical and molecular insights. Eur. J. Hum. Genet. 14, 896-903.
113. Wood, L., Gray, N. W., Zhou, Z., Green-berg, M. E., and Shepherd, G. M. (2009). Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in an RNA interference model of methyl-CpG-binding protein 2 deficiency. J. Neurosci. 29, 12440-12448.
114. Yoshii, A., and Constantine-Paton, M. (2007). BDNF induces transport ofPSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation. Nat. Neurosci. 10, 702-711.
115. Young, J. I., Hong, E. P., Castle, J. C., Crespo-Barreto, J., Bowman, A. B., Rose, M. F., Kang, D., Richman, R., Johnson, J. M., Berget, S., and Zoghbi, H. Y. (2005). Regulation of RNA splicing by the methylation-dependent transcriptional repres-sor methyl-CpG binding protein 2. Proc. Natl. Acad. Sci. U.S.A. 102, 17551-17558.
116. Zanella, S., Mebarek, S., Lajard, A. M., Picard, N., Dutschmann, M., and Hilaire, G. (2008). Oral treatment with desipramine improves breathing and life span in Rett syn drome mouse model. Respir. Physiol. Neurobiol. 160, 116-121.
117. Zheng, W.H., and Quirion, R. (2004). Comparative signaling pathways of insulin-like growth factor-1 and brain-derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival. J. Neurochem. 89, 844-852.