Mechanisms and therapeutic challenges in autism spectrum disorders: Insights from Rett syndrome

Current Opinion in Neurology

Volumn 26, Issue 2, 2013, Pages 154-159

  Castro, Jorge ^a   Mellios, Nikolaos ^a   Sur, Mriganka ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

molecular signaling pathways; monogenic disorders; neurodevelopmental disorders; pharmacological therapeutics

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID UPTAKE INHIBITOR; BRAIN DERIVED NEUROTROPHIC FACTOR; CARNITINE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; FINGOLIMOD; HYPOTHEMYCIN; MAMMALIAN TARGET OF RAPAMYCIN; METHYL CPG BINDING PROTEIN 2; MICRORNA 132; NEUROTRANSMITTER; PHENYTOIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; SEROTONIN; SOMATOMEDIN C; SOMATOSTATIN;

ANXIETY DISORDER; BLOOD BRAIN BARRIER; BRAIN DEVELOPMENT; CLINICAL FEATURE; COMMUNICATION DISORDER; COMPULSION; CONNECTOME; DEVELOPMENTAL DISORDER; DNA METHYLATION; DRUG MECHANISM; ENDOPHENOTYPE; EPIGENETICS; GASTROINTESTINAL SYMPTOM; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC CODE; GENETIC TRANSCRIPTION; GENOME IMPRINTING; GROWTH DISORDER; HUMAN; HYPOTHESIS; INTERNEURON; INTRACELLULAR SIGNALING; IRRITABILITY; MICROGLIA; NERVE CELL; NERVE CELL DIFFERENTIATION; NERVE CELL PLASTICITY; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; POSTNATAL DEVELOPMENT; PROMOTER REGION; PROTEIN DEFICIENCY; RETROPOSON; RETT SYNDROME; REVIEW; RNA SPLICING; SEIZURE; SYNAPSE;

ANIMALS; BRAIN CHEMISTRY; CHILD; CHILD DEVELOPMENT DISORDERS, PERVASIVE; DISEASE MODELS, ANIMAL; HUMANS; METHYL-CPG-BINDING PROTEIN 2; MICE; RETT SYNDROME; SYNAPSES;

EID: 84874936217     PISSN: 13507540     EISSN: 14736551     Source Type: Journal    
DOI: 10.1097/WCO.0b013e32835f19a7     Document Type: Review

References (66)

1. Pinto D, Pagnamenta AT, Klei L, et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 2010; 466:368-372.
2. Banerjee A, Castro J, Sur M. Rett syndrome: genes, synapses, circuits, and therapeutics. Front Psychiatry 2012; 3:34.
3. McGraw CM, Samaco RC, Zoghbi HY. Adult neural function requires MeCP2. Science 2011; 333:186.
4. Nguyen MV, Du F, Felice CA, et al. MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain. J Neurosci 2012; 32:10021-10034.
5. Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MeCP2, encoding methyl-CPG-binding protein 2. Nat Genet 1999; 23:185-188. (Pubitemid 29455390)
6. Guy J, Gan J, Selfridge J, et al. Reversal of neurological defects in a mouse model of Rett syndrome. Science 2007; 315:1143-1147. (Pubitemid 46328028)
7. Giacometti E, Luikenhuis S, Beard C, Jaenisch R. Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci USA 2007; 104:1931-1936. (Pubitemid 46239881)
8. Derecki NC, Cronk JC, Lu Z, et al. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 2012; 484:105-109.
9. Chang Q, Khare G, Dani V, et al. The disease progression of MeCP2 mutant mice is affected by the level of BDNF expression. Neuron 2006; 49:341-348. (Pubitemid 43152236)
10. Schmid DA, Yang T, Ogier M, et al. A TrkB small molecule partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome. J Neurosci 2012; 32:1803-1810.
11. Ogier M, Wang H, Hong E, et al. Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 2007; 27:10912-10917. (Pubitemid 47535875)
12. Johnson RA, Lam M, Punzo AM, et al. 7,8-Dihydroxyflavone exhibits therapeutic efficacy in a mouse model of Rett syndrome. J Appl Physiol 2012; 112:704-710.
13. Deogracias R, Yazdani M, Dekkers MP, et al. Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proc Natl Acad Sci USA 2012; 109:14230-14235.
14. Tropea D, Giacometti E, Wilson NR, et al. Partial reversal of Rett syndromelike symptoms in MeCP2 mutant mice. Proc Natl Acad Sci USA 2009; 106:2029-2034.
15. Castro J, Garcia R, Kwok S, et al. Functional recovery with recombinant human IGF-1 treatment in a mouse model of Rett syndrome [abstract]. In: Neuroscience 2012; 13-17 October 2012; New Orleans. Society for Neuroscience; 2012. Abstr. 246.07.
16. De Filippis B, Fabbri A, Simone D, et al. Modulation of RhoGTPases improves the behavioral phenotype and reverses astrocytic deficits in a mouse model of Rett syndrome. Neuropsychopharmacology 2012; 37:1152-1163.
17. Abdala AP, Dutschmann M, Bissonnette JM, Paton JF. Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci USA 2010; 107:18208-18213.
18. Roux JC, Dura E, Moncla A, et al. Treatment with desipramine improves breathing and survival in a mouse model for Rett syndrome. Eur J Neurosci 2007; 25:1915-1922. (Pubitemid 46581739)
19. Klose RJ, Sarraf SA, Schmiedeberg L, et al. DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CPG. Mol Cell 2005; 19:667-678. (Pubitemid 41219442)
20. Kishi N, Macklis JD. Dissecting MeCP2 function in the central nervous system. J Child Neurol 2005; 20:753-759. (Pubitemid 41498710)
21. Young JI, Hong EP, Castle JC, et al. Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CPG binding protein 2. Proc Natl Acad Sci USA 2005; 102:17551-17558. (Pubitemid 41803535)
22. Chahrour M, Jung SY, Shaw C, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008; 320:1224-1229. (Pubitemid 351929512)
23. Tudor M, Akbarian S, Chen RZ, Jaenisch R. Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain. Proc Natl Acad Sci USA 2002; 99:15536-15541. (Pubitemid 35403969)
24. Na ES, Nelson ED, Adachi M, et al. A mouse model for MeCP2 duplication syndrome: MeCP2 overexpression impairs learning and memory and synaptic transmission. J Neurosci 2012; 32:3109-3117.
25. Skene PJ, Illingworth RS, Webb S, et al. Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell 2010; 37:457-468.
26. Muotri AR,Marchetto MC, Coufal NG, et al. L1 retrotransposition in neurons is modulated by MeCP2. Nature 2010; 468:443-446.
27. LaSalle JM. The odyssey of MeCP2 and parental imprinting. Epigenetics 2007; 2:5-10.
28. De Leon-Guerrero SD, Pedraza-Alva G, Perez-Martinez L. In sickness and in health: the role of methyl-CPG binding protein 2 in the central nervous system. Eur J Neurosci 2011; 33:1563-1574.
29. Klein ME, Lioy DT, Ma L, et al. Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA. Nat Neurosci 2007; 10:1513-1514. (Pubitemid 350175879)
30. Wu H, Tao J, Chen PJ, et al. Genome-wide analysis reveals methyl-CPGbinding protein 2-dependent regulation of microRNAs in a mouse model of Rett syndrome. Proc Natl Acad Sci USA 2010; 107:18161-18166.
31. Urdinguio RG, Fernandez AF, Lopez-Nieva P, et al. Disrupted microRNA expression caused by MeCP2 loss in a mouse model of Rett syndrome. Epigenetics 2010; 5:656-663.
32. Mellios N, Sugihara H, Castro J, et al. miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity. Nat Neurosci 2011; 14:1240-1242.
33. Tognini P, Putignano E, Coatti A, Pizzorusso T. Experience-dependent expression of miR-132 regulates ocular dominance plasticity. Nat Neurosci 2011; 14:1237-1239.
34. Im HI, Hollander JA, Bali P, Kenny PJ. MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nat Neurosci 2010; 13:1120-1127.
35. Lonze BE, Ginty DD. Function and regulation of CREB family transcription factors in the nervous system. Neuron 2002; 35:605-623. (Pubitemid 35229980)
36. Sayed D, Abdellatif M. Akt-ing via microRNA. Cell Cycle 2010; 9:3213-3217.
37. Fornari F, Milazzo M, Chieco P, Gramantieri L. miR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res 2010; 70:5184-5193.
38. Nomura T, Kimura M, Horii T, et al. MeCP2-dependent repression of an imprinted miR-184 released by depolarization. Hum Mol Genet 2008; 17:1192-1199. (Pubitemid 351494191)
39. Ballas N, Lioy DT, Grunseich C, Mandel G. Noncell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci 2009; 12:311-317.
40. Maezawa I, Swanberg S, Harvey D, et al. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci 2009; 29:5051-5061.
41. Lioy DT, Garg SK, Monaghan CE, et al. A role for glia in the progression of Rett's syndrome. Nature 2011; 475:497-500.
42. Maezawa I, Jin LW. Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J Neurosci 2010; 30:5346-5356.
43. Chao HT, Chen H, Samaco RC, et al. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 2010; 468:263-269.
44. Samaco RC, Nagarajan RP, Braunschweig D, LaSalle JM. Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Hum Mol Genet 2004; 13:629-639. (Pubitemid 38379852)
45. Kishi N, Macklis JD. MeCP2 is progressively expressed in postmigratory neurons and is involved in neuronal maturation rather than cell fate decisions. MolCell Neurosci 2004; 27:306-321. (Pubitemid 39433843)
46. Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY. Insight into Rett syndrome: MeCP2 levels display tissue-and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 2002; 11:115-124. (Pubitemid 34157003)
47. Chao HT, Zoghbi HY, Rosenmund C. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron 2007; 56:58-65. (Pubitemid 47484176)
48. Dani VS, Nelson SB. Intact long-term potentiation but reduced connectivity between neocortical layer 5 pyramidal neurons in a mouse model of Rett syndrome. J Neurosci 2009; 29:11263-11270.
49. Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol 2005; 20:747-753. (Pubitemid 41498709)
50. Belichenko PV, Wright EE, Belichenko NP, et al. Widespread changes in dendritic and axonal morphology in MeCP2-mutant mouse models of Rett syndrome: Evidence for disruption of neuronal networks. J Comp Neurol 2009; 514:240-258.
51. Kline DD, Ogier M, Kunze DL, Katz DM. Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in MeCP2-null mice. J Neurosci 2010; 30:5303-5310.
52. Abuhatzira L, Makedonski K, Kaufman Y, et al. MeCP2 deficiency in the brain decreases BDNF levels by REST/CoREST-mediated repression and increases TrkB production. Epigenetics 2007; 2:214-222. (Pubitemid 351308296)
53. Yoshii A, Constantine-Paton M. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol 2010; 70:304-322.
54. Deak F, Sonntag WE. Aging, synaptic dysfunction, and insulin-like growth factor (IGF)-1. J Gerontol A Biol Sci Med Sci 2012; 67:611-625.
55. Ricciardi S, Boggio EM, Grosso S, et al. Reduced Akt/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model. Hum Mol Genet 2011; 20:1182-1196.
56. Yoshii A, Constantine-Paton M. BDNF induces transport of PSD-95 to dendrites through PI3K-Akt signaling after NMDA receptor activation. Nat Neurosci 2007; 10:702-711. (Pubitemid 46828509)
57. Kumar V, Zhang MX, Swank MW, et al. Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways. J Neurosci 2005; 25:11288-11299. (Pubitemid 43083703)
58. Cuesto G, Enriquez-Barreto L, Carames C, et al. Phosphoinositide-3-kinase activation controls synaptogenesis and spinogenesis in hippocampal neurons. J Neurosci 2011; 31:2721-2733.
59. Tolias KF, Duman JG, Um K. Control of synapse development and plasticity by Rho GTPase regulatory proteins. Prog Neurobiol 2011; 94:133-148.
60. Viemari JC, Roux JC, Tryba AK, et al. MeCP2 deficiency disrupts norepinephrine and respiratory systems in mice. J Neurosci 2005; 25:11521-11530. (Pubitemid 43098445)
61. Medrihan L, Tantalaki E, Aramuni G, et al. Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome. J Neurophysiol 2008; 99:112-121.
62. McCauley MD, Wang T, Mike E, et al. Pathogenesis of lethal cardiac arrhythmias in MeCP2 mutant mice: Implication for therapy in Rett syndrome. Sci Transl Med 2011; 3:113ra125.
63. Schaevitz LR, D'Iddio E, Iannoni R, et al. Acetyl-L-carnitine improves behavioral and dendritic morphology abnormalities in a mouse model of Rett syndrome [abstract]. In: Neuroscience 2011; 12-16 November 2011; Washington DC. Society for Neuroscience; 2011. Abstr. 849.05.
64. Ellaway CJ, Peat J, Williams K, et al. Medium-term open label trial of L-carnitine in Rett syndrome. Brain Dev 2001; 23 (Suppl. 1):S85-S89.
65. Grosser E, Hirt U, Janc OA, et al. Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome. Neurobiol Dis 2012; 48:102-114.
66. De Felice C, Signorini C, Leoncini S, et al. The role of oxidative stress in Rett syndrome: an overview. Ann N Y Acad Sci 2012; 1259:121-135.