Abstract
Rett syndrome (RTT) is a severe postnatal neurological disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. In affected children, most biological parameters, including brain structure, are normal (although acquired microcephaly is usually present). However, in recent years, a deficit in bioaminergic metabolism has been identified at the cellular and molecular levels, in more than 200 patients. Recently available transgenic mouse strains with a defective Mecp2 gene also show abnormalities, strongly suggesting that there is a direct link between the function of the MECP2 protein and the metabolism of biogenic amines. Biogenic amines appear to have an important role in the pathophysiology of Rett syndrome, for several reasons. Firstly, biogenic amines modulate a large number of autonomic and cognitive functions. Secondly, many of these functions are affected in RTT patients. Thirdly, biogenic amines are the only neurotransmitters that have repeatedly been found to be altered in RTT patients. Importantly, pharmacological interventions can be envisaged to try to counteract the deficits observed. Here, we review the available human and mouse data and present how they have been and could be used in the development of pharmacological treatments for children affected by the syndrome. Given our current knowledge and the tools available, modulating biogenic amine metabolism may prove to be the most promising strategy for improving the life quality of Rett syndrome patients in the short term.
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Abuhatzira L, Makedonski K, Kaufman Y, Razin A, Shemer R (2007) MeCP2 deficiency in the brain decreases BDNF levels by REST/CoREST-mediated repression and increases TRKB production. Epigenetics 2(4):214–222
Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23(2):185–188
Amir R, Dahle EJ, Toriolo D, Zoghbi HY (2000) Candidate gene analysis in Rett syndrome and the identification of 21 SNPs in Xq. Am J Med Genet 90(1):69–71
Amir RE, Sutton VR, Van den Veyver IB (2005) Newborn screening and prenatal diagnosis for Rett syndrome: implications for therapy. J Child Neurol 20(9):779–783
Andaku DK, Mercadante MT, Schwartzman JS (2005) Buspirone in Rett syndrome respiratory dysfunction. Brain Dev 27(6):437–438
Archer HL, Evans J, Edwards S, Colley J, Newbury-Ecob R, O’Callaghan F, Huyton M, O’Regan M, Tolmie J, Sampson J, Clarke A, Osborne J (2006) CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet 43:729–734
Ariani F, Hayek G, Rondinella D, Artuso R, Mencarelli MA, Spanhol-Rosseto A, Pollazzon M, Buoni S, Spiga O, Ricciardi S, Meloni I, Longo I, Mari F, Broccoli V, Zappella M, Renieri A (2008) FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet 83(1):89–93
Armstrong DD (1997) Review of Rett syndrome. J Neuropathol Exp Neurol 56(8):843–849
Armstrong DD (2001) Rett syndrome neuropathology review 2000. Brain Dev 23S1:S72–S76
Armstrong DD (2002) Neuropathology of Rett syndrome. Ment Retard Dev Disabil Res Rev 8(2):72–76
Azmitia EC (2001) Neuronal instability: implications for Rett’s syndrome. Brain Dev 23S1:S1–S10
Bahi-Buisson N, Nectoux J, Rosas-Vargas H, Milh M, Boddaert N, Girard B, Cances C, Ville D, Afenjar A, Rio M, Héron D, N’guyen Morel MA, Arzimanoglou A, Philippe C, Jonveaux P, Chelly J, Bienvenu T (2008) Key clinical features to identify girls with CDKL5 mutations. Brain 131:2647–2661
Baruch P, Artaud F, Godeheu G, Barbeito L, Glowinski J, Chéramy A (1988) Substance P and neurokinin A regulate by different mechanisms dopamine release from dendrites and nerve terminals of the nigrostriatal dopaminergic neurons. Neuroscience 25(3):889–898
Bauman ML, Kemper TL, Arin DM (1995) Pervasive neuroanatomic abnormalities of the brain in three cases of Rett’s syndrome. Neurology 45(8):1581–1586
Ben Zeev B, Bebbington A, Ho G, Leonard H, de Klerk N, Gak E, Vecsler M, Christodoulou J (2009) The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome. Neurology 72(14):1242–1247
Bissonnette JM, Knopp SJ (2008) Effect of inspired oxygen on periodic breathing in methy-CpG-binding protein 2 (Mecp2) deficient mice. J Appl Physiol 104(1):198–204
Boltshauser E, Niederwieser A, Kierat L, Haenggeli CA (1986) Pterins in patients with Rett syndrome. Am J Med Genet S1:317–321
Bräutigam C, Steenbergen-Spanjers GC, Hoffmann GF, Dionisi-Vici C, van den Heuvel LP, Smeitink JA, Wevers RA (1999) Biochemical and molecular genetic characteristics of the severe form of tyrosine hydroxylase deficiency. Clin Chem 45(12):2073–2078
Breese GR, Baumeister A, Napier TC, Frye GD, Mueller RA (1985) Evidence that D-1 dopamine receptors contribute to the supersensitive behavioral responses induced by L-dihydroxyphenylalanine in rats treated neonatally with 6-hydroxydopamine. J Pharmacol Exp Ther 235(2):287–295
Brero A, Easwaran HP, Nowak D, Grunewald I, Cremer T, Leonhardt H, Cardoso MC (2005) Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation. J Cell Biol 169(5):733–743
Brücke T, Sofic E, Killian W, Rett A, Riederer P (1987) Reduced concentrations and increased metabolism of biogenic amines in a single case of Rett-syndrome: a postmortem brain study. J Neural Transm 68(3–4):315–324
Burd L, Kemp R, Knull H, Loveless D (1990) A review of the biochemical pathways studied and abnormalities reported in the Rett syndrome. Brain Dev 12(4):444–448
Burroni L, Aucone AM, Volterrani D, Hayek Y, Bertelli P, Vella A, Zappella M, Vattimo A (1997) Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD. Nucl Med Commun 18(6):527–534
Carter JC, Lanham DC, Pham D, Bibat G, Naidu S, Kaufmann WE (2008) Selective cerebral volume reduction in Rett syndrome: a multiple-approach MR imaging study. AJNR Am J Neuroradiol 29(3):436–441
Casanova MF, Naidu S, Goldberg TE, Moser HW, Khoromi S, Kumar A, Kleinman JE, Weinberger DR (1991) Quantitative magnetic resonance imaging in Rett syndrome. J Neuropsychiatry Clin Neurosci 3(1):66–72
Cassel S, Carouge D, Gensburger C, Anglard P, Burgun C, Dietrich JB, Aunis D, Zwiller J (2006) Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain. Mol Pharmacol 70(2):487–492
Chadwick LH, Wade PA (2007) MeCP2 in Rett syndrome: transcriptional repressor or chromatin architectural protein? Curr Opin Genet Dev 17(2):121–125
Chahrour M, Zoghbi HY (2007) The story of Rett syndrome: from clinic to neurobiology. Neuron 56(3):422–437
Chang Q, Khare G, Dani V, Nelson S, Jaenisch R (2006) The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49(3):341–348
Chen RZ, Akbarian S, Tudor M, Jaenisch R (2001) Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet 27(3):327–331
Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, Jaenisch R, Greenberg ME (2003) Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302(5646):885–889
Chiron C, Bulteau C, Loc’h C, Raynaud C, Garreau B, Syrota A, Mazière B (1993) Dopaminergic D2 receptor SPECT imaging in Rett syndrome: increase of specific binding in striatum. J Nucl Med 34(10):1717–1721
Cirignotta F, Lugaresi E, Montagna P (1986) Breathing impairment in Rett syndrome. Am J Med Genet S1:167–173
Cornford ME, Philippart M, Jacobs B, Scheibel AB, Vinters HV (1994) Neuropathology of Rett syndrome: case report with neuronal and mitochondrial abnormalities in the brain. J Child Neurol 9(4):424–431
David HN, Ansseau M, Abraini JH (2005) Dopamine-glutamate reciprocal modulation of release and motor responses in the rat caudate-putamen and nucleus accumbens of “intact” animals. Brain Res Brain Res Rev 50(2):336–360
Deguchi K, Antalffy BA, Twohill LJ, Chakraborty S, Glaze DG, Armstrong DD (2000) Substance P immunoreactivity in Rett syndrome. Pediatr Neurol 22(4):259–266
Dionisi-Vici C, Hoffmann GF, Leuzzi V, Hoffken H, Bräutigam C, Rizzo C, Steebergen-Spanjers GC, Smeitink JA, Wevers RA (2000) Tyrosine hydroxylase deficiency with severe clinical course: clinical and biochemical investigations and optimization of therapy. J Pediatr 136(4):560–562
Do T, Kerr B, Kuzhikandathil EV (2007) Brain-derived neurotrophic factor regulates the expression of D1 dopamine receptors. J Neurochem 100(2):416–428
Dotti MT, Guideri F, Acampa M, Orrico A, Battisti C, Federico A (2004) Autonomic dysfunction in mental retardation and spastic paraparesis with MECP2 mutation. J Child Neurol 19(12):964–966
Dunn HG, Stoessl AJ, Ho HH, MacLeod PM, Poskitt KJ, Doudet DJ, Schulzer M, Blackstock D, Dobko T, Koop B, de Amorim GV (2002) Rett syndrome: investigation of nine patients, including PET scan. Can J Neurol Sci 29(4):345–357
Ebner K, Singewald N (2007) Stress-induced release of substance P in the locus coeruleus modulates cortical noradrenaline release. Naunyn Schmiedebergs Arch Pharmacol 376(1–2):73–82
Elia M, Falco M, Ferri R, Spalletta A, Bottitta M, Calabrese G, Carotenuto M, Musumeci SA, Lo Giudice M, Fichera M (2008) CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy. Neurology 71(13):997–999
Fitzgerald PM, Jankovic J, Percy AK (1990) Rett syndrome and associated movement disorders. Mov Disord 5(3):195–202
Fiumara A, Sciotto A, Barone R, D’Asero G, Munda S, Parano E, Pavone L (1999) Peripheral lymphocyte subsets and other immune aspects in Rett syndrome. Pediatr Neurol 21(3):619–621
Glaze DG (2005) Neurophysiology of Rett syndrome. J Child Neurol 20(9):740–746
Glaze DG, Percy AK, Motil KJ, Lane JB, Isaacs JS, Schultz RJ, Barrish JO, Neul JL, O’Brien WE, Smith EO (2009) A study of the treatment of Rett syndrome with folate and betaine. J Child Neurol 24(5):551–556
Gökcay A, Kitis O, Ekmekci O, Karasoy H, Sener RN (2002) Proton MR spectroscopy in Rett syndrome. Comput Med Imaging Graph 26(4):271–275
Gospe SM Jr, Gietzen DW, Summers PJ, Lunetta JM, Miller JW, Selhub J, Ellis WG, Clifford AJ (1995) Behavioral and neurochemical changes in folate-deficient mice. Physiol Behav 58(5):935–941
Guideri F, Acampa M, Blardi P, de Lalla A, Zappella M, Hayek Y (2004) Cardiac dysautonomia and serotonin plasma levels in Rett syndrome. Neuropediatrics 35(1):36–38
Guy J, Hendrich B, Holmes M, Martin JE, Bird A (2001) A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27(3):322–326
Guy J, Gan J, Selfridge J, Cobb S, Bird A (2007) Reversal of neurological defects in a mouse model of Rett syndrome. Science 315(5815):1143–1147
Hagberg B, Aicardi J, Dias K, 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(4):471–479
Hagberg B, Hanefeld F, Percy A, Skjeldal O (2002) An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett syndrome clinical criteria consensus panel satellite to European paediatric neurology society meeting, Baden Baden, Germany, 11 September 2001. Eur J Paediatr Neurol 6(5):293–297
Hanefeld F, Christen HJ, Holzbach U, Kruse B, Frahm J, Hänicke W (1995) Cerebral proton magnetic resonance spectroscopy in Rett syndrome. Neuropediatrics 26(2):126–127
Harding BN, Tudway AJ, Wilson J (1985) Neuropathological studies in a child showing some features of the Rett syndrome. Brain Dev 7(3):342–344
Harris JC, Wong DF, Wagner HN Jr, Rett A, Naidu S, Dannals RF, Links JM, Batshaw ML, Moser HW (1986) Positron emission tomographic study of D2 dopamine receptor binding and CSF biogenic amine metabolites in Rett syndrome. Am J Med Genet S1:201–210
Hébert JM, Fishell G (2008) The genetics of early telencephalon patterning: some assembly required. Nat Rev Neurosci 9(9):678–685
Horike S, Cai S, Miyano M, Cheng JF, Kohwi-Shigematsu T (2005) Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet 37(1):31–40
Horská A, Naidu S, Herskovits EH, Wang PY, Kaufmann WE, Barker PB (2000) Quantitative 1H MR spectroscopic imaging in early Rett syndrome. Neurology 54(3):715–722
Hou L, Tang H, Chen Y, Wang L, Zhou X, Rong W, Wang J (2009) Presynaptic modulation of tonic and respiratory inputs to cardiovagal motoneurons by substance P. Brain Res 1284:31–40
Huppke P, Held M, Laccone F, Hanefeld F (2003) The spectrum of phenotypes in females with Rett syndrome. Brain Dev 25(5):346–351
Ide S, Itoh M, Goto Y (2005) Defect in normal developmental increase of the brain biogenic amine concentrations in the mecp2-null mouse. Neurosci Lett 386(1):14–17
Jankovic J (2008) Parkinson’s disease and movement disorders: moving forward. Lancet Neurol 7(1):9–11
Jellinger KA (2003) Rett syndrome—an update. J Neural Transm 110(6):681–701
Jellinger K, Seitelberger F (1986) Neuropathology of Rett syndrome. Am J Med Genet 25S1:259–270
Jellinger K, Armstrong D, Zoghbi HY, Percy AK (1988) Neuropathology of Rett syndrome. Acta Neuropathol 76:142–158
Johnston MV, Hohmann C, Blue ME (1995) Neurobiology of Rett syndrome. Neuropediatrics 26(2):119–122
Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M (2009) Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J Neurosci 29(27):8688–8697
Julu PO, Kerr AM, Hansen S, Apartopoulos F, Jamal GA (1997) Functional evidence of brain stem immaturity in Rett syndrome. Eur Child Adolesc Psychiatry 6S1:47–54
Kameshita I, Sekiguchi M, Hamasaki D, Sugiyama Y, Hatano N, Suetake I, Tajima S, Sueyoshi N (2008) Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1. Biochem Biophys Res Commun 377(4):1162–1167
Kitt CA, Wilcox BJ (1995) Preliminary evidence for neurodegenerative changes in the substantia nigra of Rett syndrome. Neuropediatrics 26(2):114–118
Kitt CA, Troncoso JC, Price DL, Naidu S, Moser HW (1990) Pathological changes in substantia nigra and basal forebrain neurons in Rett syndrome. Ann Neurol 28(3):S6
Kondo M, Gray LJ, Pelka GJ, Christodoulou J, Tam PP, Hannan AJ (2008) Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome—Mecp2 gene dosage effects and BDNF expression. Eur J Neurosci 27(12):3342–3350
Krägeloh-Mann I, Schroth G, Niemann G, Michaelis R (1989) The Rett syndrome: magnetic resonance imaging and clinical findings in four girls. Brain Dev 11(3):175–178
Kumar A, Choi KH, Renthal W, Tsankova NM, Theobald DE, Truong HT, Russo SJ, Laplant Q, Sasaki TS, Whistler KN, Neve RL, Self DW, Nestler EJ (2005) Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48(2):303–314
Ladas T, Chan SA, Ogier M, Smith C, Katz DM (2009) Enhanced dense core granule function and adrenal hypersecretion in a mouse model of Rett syndrome. Eur J Neurosci 30(4):602–610
Lauterborn JC, Truong GS, Baudry M, Bi X, Lynch G, Gall CM (2003) Chronic elevation of brain-derived neurotrophic factor by ampakines. J Pharmacol Exp Ther 307(1):297–305
Lekman A, Witt-Engerström I, Gottfries J, Hagberg BA, Percy AK, Svennerholm L (1989) Rett syndrome: biogenic amines and metabolites in postmortem brain. Pediatr Neurol 5(6):357–362
Lekman A, Witt-Engerström I, Holmberg B, Percy A, Svennerholm L, Hagberg B (1990) CSF and urine biogenic amine metabolites in Rett syndrome. Clin Genet 37(3):173–178
Leontovich TA, Mukhina JK, Fedorov AA, Belichenko PV (1999) Morphological study of the entorhinal cortex, hippocampal formation, and basal ganglia in Rett syndrome patients. Neurobiol Dis 6(2):77–91
Leuzzi V, Di Sabato ML, Zollino M, Montanaro ML, Seri S (2004) Early-onset encephalopathy and cortical myoclonus in a boy with MECP2 gene mutation. Neurology 63(10):1968–1970
Loupe PS, Bredemeier JD, Schroeder SR, Tessel RE (2002) Dopamine re-uptake inhibitor GBR-12909 induction of aberrant behaviors in animal models of dopamine dysfunction. Int J Dev Neurosci 20(3–5):323–333
Lüdecke B, Dworniczak B, Bartholomé K (1995) A point mutation in the tyrosine hydroxylase gene associated with Segawa’s syndrome. Hum Genet 95(1):123–125
Luikenhuis S, Giacometti E, Beard CF, Jaenisch R (2004) Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci USA 101(16):6033–6038
Makedonski K, Abuhatzira L, Kaufman Y, Razin A, Shemer R (2005) MeCP2 deficiency in Rett syndrome causes epigenetic aberrations at the PWS/AS imprinting center that affects UBE3A expression. Hum Mol Genet 14(8):1049–1058
Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Hayek G, Balestri P, Bergo A, Badaracco G, Zappella M, Broccoli V, Renieri A, Kilstrup-Nielsen C, Landsberger N (2005) CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet 14(14):1935–1946
Marín-Valencia I, Serrano M, Ormazabal A, Pérez-Dueñas B, García-Cazorla A, Campistol J, Artuch R (2008) Biochemical diagnosis of dopaminergic disturbances in paediatric patients: analysis of cerebrospinal fluid homovanillic acid and other biogenic amines. Clin Biochem 41(16–17):1306–1315
Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302(5646):890–893
Matarazzo V, Cohen D, Palmer AM, Simpson PJ, Khokhar B, Pan SJ, Ronnett GV (2004) The transcriptional repressor Mecp2 regulates terminal neuronal differentiation. Mol Cell Neurosci 27(1):44–58
Matsuishi T, Nagamitsu S, Yamashita Y, Murakami Y, Kimura A, Sakai T, Shoji H, Kato H, Percy AK (1997) Decreased cerebrospinal fluid levels of substance P in patients with Rett syndrome. Ann Neurol 42(6):978–981
McArthur AJ, Budden SS (1998) Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol 40(3):186–192
Menheniott TR, Woodfine K, Schulz R, Wood AJ, Monk D, Giraud AS, Baldwin HS, Moore GE, Oakey RJ (2008) Genomic imprinting of Dopa decarboxylase in heart and reciprocal allelic expression with neighboring Grb10. Mol Cell Biol 28(1):386–396
Miyamoto A, Oki J, Takahashi S, Okuno A (1999) Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome. Brain Dev 21(1):59–62
Mora F, Segovia G, del Arco A (2007) Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain. Brain Res Rev 55(1):78–88
Muhle R, Trentacoste SV, Rapin I (2004) The genetics of autism. Pediatrics 113(5):e472–e486
Murakami JW, Courchesne E, Haas RH, Press GA, Yeung-Courchesne R (1992) Cerebellar and cerebral abnormalities in Rett syndrome: a quantitative MR analysis. AJR Am J Roentgenol 159(1):177–183
Nag N, Moriuchi JM, Peitzman CG, Ward BC, Kolodny NH, Berger-Sweeney JE (2009) Environmental enrichment alters locomotor behaviour and ventricular volume in Mecp2 1lox mice. Behav Brain Res 196(1):44–48
Naidu S, Wong DF, Kitt C, Wenk G, Moser HW (1992) Positron emission tomography in the Rett syndrome: clinical, biochemical and pathological correlates. Brain Dev 14S:S75–S79
Naidu S, Kaufmann WE, Abrams MT, Pearlson GD, Lanham DC, Fredericksen KA, Barker PB, Horska A, Golay X, Mori S, Wong DF, Yablonski M, Moser HW, Johnston MV (2001) Neuroimaging studies in Rett syndrome. Brain Dev 23S1:62–71
Namihira M, Nakashima K, Taga T (2004) Developmental stage dependent regulation of DNA methylation and chromatin modification in a immature astrocyte specific gene promoter. FEBS Lett 572(1–3):184–188
Nectoux J, Bahi-Buisson N, Guellec I, Coste J, De Roux N, Rosas H, Tardieu M, Chelly J, Bienvenu T (2008) The p.Val66Met polymorphism in the BDNF gene protects against early seizures in Rett syndrome. Neurology 70(22 Pt 2):2145–2151
Nielsen JB, Lou HC, Andresen J (1990) Biochemical and clinical effects of tyrosine and tryptophan in the Rett syndrome. Brain Dev 12(1):143–147
Nielsen JB, Bertelsen A, Lou HC (1992) Low CSF HVA levels in the Rett syndrome: a reflection of restricted synapse formation? Brain Dev 14S:S63–S65
Nielsen JB, Toft PB, Reske-Nielsen E, Jensen KE, Christiansen P, Thomsen C, Henriksen O, Lou HC (1993) Cerebral magnetic resonance spectroscopy in Rett syndrome. Failure to detect mitochondrial disorder. Brain Dev 15(2):107–112
Nihei K, Naitoh H (1990) Cranial computed tomographic and magnetic resonance imaging studies on the Rett syndrome. Brain Dev 12(1):101–105
Nomura Y, Segawa M, Higurashi M (1985) Rett syndrome—an early catecholamine and indolamine deficient disorder? Brain Dev 7(3):334–341
Nomura Y, Kimura K, Arai H, Segawa M (1997) Involvement of the autonomic nervous system in the pathophysiology of Rett syndrome. Eur Child Adolesc Psychiatry 6S1:42–46
Oehme P, Hecht K, Faulhaber HD, Nieber K, Roske I, Rathsack R (1987) Relationship of substance P to catecholamines, stress, and hypertension. J Cardiovasc Pharmacol 10S12:S109–S111
Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM (2007) Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 27(40):10912–10917
Okado N, Narita M, Narita N (2001) A biogenic amine-synapse mechanism for mental retardation and developmental disabilities. Brain Dev 23S1:S11–S15
Ormazabal A, Artuch R, Vilaseca MA, Aracil A, Pineda M (2005) Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Neuropediatrics 36(6):380–385
Pan JW, Lane JB, Hetherington H, Percy AK (1999) Rett syndrome: 1H spectroscopic imaging at 4.1 Tesla. J Child Neurol 14(8):524–528
Paterson DS, Thompson EG, Belliveau RA, Antalffy BA, Trachtenberg FL, Armstrong DD, Kinney HC (2005) Serotonin transporter abnormality in the dorsal motor nucleus of the vagus in Rett syndrome: potential implications for clinical autonomic dysfunction. J Neuropathol Exp Neurol 64(11):1018–1027
Pelligra R, Norton RD, Wilkinson R, Leon HA, Matson WR (1992) Rett syndrome: stimulation of endogenous biogenic amines. Neuropediatrics 23(3):131–137
Peña F, Ramirez JM (2004) Substance P-mediated modulation of pacemaker properties in the mammalian respiratory network. J Neurosci 24(34):7549–7556
Percy AK, Zoghbi H, Riccardi VM (1985) Rett syndrome: initial experience with an emerging clinical entity. Brain Dev 7(3):300–304
Perry TL, Dunn HG, Ho HH, Crichton JU (1988) Cerebrospinal fluid values for monoamine metabolites, gamma-aminobutyric acid, and other amino compounds in Rett syndrome. J Pediatr 112(2):234–238
Piazza CC, Fisher W, Kiesewetter K, Bowman L, Moser H (1990) Aberrant sleep patterns in children with the Rett syndrome. Brain Dev 12(5):488–493
Plioplys AV, Greaves A, Kazemi K, Silverman E (1994) Lymphocyte function in autism and Rett syndrome. Neuropsychobiology 29(1):12–16
Porritt MJ, Batchelor PE, Howells DW (2005) Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons. Exp Neurol 192(1):226–234
Presti MF, Gibney BC, Lewis MH (2004) Effects of intrastriatal administration of selective dopaminergic ligands on spontaneous stereotypy in mice. Physiol Behav 80(4):433–439
Ramaekers VT, Hansen SI, Holm J, Opladen T, Senderek J, Häusler M, Heimann G, Fowler B, Maiwald R, Blau N (2003) Reduced folate transport to the CNS in female Rett patients. Neurology 61(4):506–515
Reiss AL, Faruque F, Naidu S, Abrams M, Beaty T, Bryan RN, Moser H (1993) Neuroanatomy of Rett syndrome: a volumetric imaging study. Ann Neurol 34(2):227–234
Rett A (1966) On a unusual brain atrophy syndrome in hyperammonemia in childhood. Wien Med Wochenschr 116(37):723–726
Rett A (1977) Cerebral atrophy associated with hyperammonaemia. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 29. Elsevier, Amsterdam, pp 305–329
Ricceri L, De Filippis B, Laviola G (2008) Mouse models of Rett syndrome: from behavioural phenotyping to preclinical evaluation of new therapeutic approaches. Behav Pharmacol 19(5–6):501–517
Riederer P, Brücke T, Sofic E, Kienzl E, Schnecker K, Schay V, Kruzik P, Killian W, Rett A (1985) Neurochemical aspects of the Rett syndrome. Brain Dev 7(3):351–360
Riederer P, Weiser M, Wichart I, Schmidt B, Killian W, Rett A (1986) Preliminary brain autopsy findings in progredient Rett syndrome. Am J Med Genet S1:305–315
Riikonen R, Vanhala R (1999) Levels of cerebrospinal fluid nerve-growth factor differ in infantile autism and Rett syndrome. Dev Med Child Neurol 41(3):148–152
Roux JC, Dura E, Moncla A, Mancini J, Villard L (2007) Treatment with desipramine improves breathing and survival in a mouse model for Rett syndrome. Eur J Neurosci 25(7):1915–1922
Roux JC, Dura E, Villard L (2008) Tyrosine hydroxylase deficit in the chemoafferent and the sympathoadrenergic pathways of the Mecp2 deficient mouse. Neurosci Lett 447(1):82–86
Sahota A, Leeming R, Blair J, Hagberg B (1985) Tetrahydrobiopterin metabolism in the Rett disease. Brain Dev 7(3):249–250
Saito Y, Ito M, Ozawa Y, Matsuishi T, Hamano K, Takashima S (2001) Reduced expression of neuropeptides can be related to respiratory disturbances in Rett syndrome. Brain Dev 23S1:S122–S126
Sasaki H, Ishihara K, Kato R (2000) Mechanisms of Igf2/H19 imprinting: DNA methylation, chromatin and long-distance gene regulation. J Biochem 127(5):711–715
Satoi M, Matsuishi T, Yamada S, Yamashita Y, Ohtaki E, Mori K, Riikonen R, Kato H, Percy AK (2000) Decreased cerebrospinal fluid levels of beta-phenylethylamine in patients with Rett syndrome. Ann Neurol 47(6):801–803
Schanen NC, Dahle EJ, Capozzoli F, Holm VA, Zoghbi HY, Francke U (1997) A new Rett syndrome family consistent with X-linked inheritance expands the X chromosome exclusion map. Am J Hum Genet 61(3):634–641
Seeman P, Bzowej NH, Guan HC, Bergeron C, Becker LE, Reynolds GP, Bird ED, Riederer P, Jellinger K, Watanabe S, Tourtellotte WW (1987) Human brain dopamine receptors in children and aging adults. Synapse 1(5):399–404
Segawa M (2001) Pathophysiology of Rett syndrome from the stand point of clinical characteristics. Brain Dev 23S1:S94–S98
Seroogy KB, Lundgren KH, Tran TM, Guthrie KM, Isackson PJ, Gall CM (1994) Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs. J Comp Neurol 342(3):321–334
Shadrina MI, Dolotov OV, Grivennikov IA, Slominsky PA, Andreeva LA, Inozemtseva LS, Limborska SA, Myasoedov NF (2001) Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog. Neurosci Lett 308:115–118
Shahbazian MD, Sun Y, Zoghbi HY (2002) Balanced X chromosome inactivation patterns in the Rett syndrome brain. Am J Med Genet 111(2):164–168
Sirianni N, Naidu S, Pereira J, Pillotto RF, Hoffman EP (1998) Rett syndrome: confirmation of X-linked dominant inheritance, and localization of the gene to Xq28. Am J Hum Genet 63(5):1552–1558
Solaas KM, Skjeldal O, Gardner ML, Kase FB, Reichelt KL (2002) Urinary peptides in Rett syndrome. Autism 6(3):315–328
Suzuki H (1991) Bromocriptine improves circadian rhythm in Rett syndrome. No To Hattatsu 23(2):213–214
Temudo T, Rios M, Prior C, Carrilho I, Santos M, Maciel P, Sequeiros J, Fonseca M, Monteiro J, Cabral P, Vieira JP, Ormazabal A, Artuch R (2009) Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment. Brain Dev 31(1):46–51
Tsai SJ (2007) Semax, an analogue of adrenocorticotropin (4–10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Med Hypotheses 68(5):1144–1146
Urdinguio RG, Lopez-Serra L, Lopez-Nieva P, Alaminos M, Diaz-Uriarte R, Fernandez AF, Esteller M (2008) Mecp2-null mice provide new neuronal targets for Rett syndrome. PLoS One 3(11):e3669
Verbeek MM, Blom AM, Wevers RA, Lagerwerf AJ, van de Geer J, Willemsen MA (2008) Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations. Mol Genet Metab 95(3):127–132
Viemari JC, Roux JC, Tryba AK, Saywell V, Burnet H, Peña F, Zanella S, Bévengut M, Barthelemy-Requin M, Herzing LB, Moncla A, Mancini J, Ramirez JM, Villard L, Hilaire G (2005) Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. J Neurosci 25(50):11521–11530
Voituron N, Zanella S, Menuet C, Dutschmann M, Hilaire G (2009) Early breathing defects after moderate hypoxia or hypercapnia in a mouse model of Rett syndrome. Respir Physiol Neurobiol 168:109–118
Wang H, Chan SA, Ogier M, Hellard D, Wang Q, Smith C, Katz DM (2006) Dysregulation of brain-derived neurotrophic factor expression and neurosecretory function in Mecp2 null mice. J Neurosci 26(42):10911–10915
Wenk GL (1995) Alterations in dopaminergic function in Rett syndrome. Neuropediatrics 26(2):123–125
Wenk GL (1996) Rett syndrome: evidence for normal dopaminergic function. Neuropediatrics 27(5):256–259
Wenk GL, Naidu S, Casanova MF, Kitt CA, Moser H (1991) Altered neurochemical markers in Rett’s syndrome. Neurology 41(11):1753–1756
Wilken B, Lalley P, Bischoff AM, Christen HJ, Behnke J, Hanefeld F, Richter DW (1997) Treatment of apneustic respiratory disturbance with a serotonin-receptor agonist. J Pediatr 130(1):89–94
Williamson SL, Christodoulou J (2006) Rett syndrome: new clinical and molecular insights. Eur J Hum Genet 14(8):896–903
Wong DF, Harris JC, Naidu S, Yokoi F, Marenco S, Dannals RF, Ravert HT, Yaster M, Evans A, Rousset O, Bryan RN, Gjedde A, Kuhar MJ, Breese GR (1996) Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo. Proc Natl Acad Sci USA 93(11):5539–5543
Wong DF, Ricaurte G, Gründer G, Rothman R, Naidu S, Singer H, Harris J, Yokoi F, Villemagne V, Szymanski S, Gjedde A, Kuhar M (1997) Dopamine transporter changes in neuropsychiatric disorders. Adv Pharmacol 42:219–223
Yasui DH, Peddada S, Bieda MC, Vallero RO, Hogart A, Nagarajan RP, Thatcher KN, Farnham PJ, Lasalle JM (2007) Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci USA 104(49):19416–19421
Zanella S, Mebarek S, Lajard AM, Picard N, Dutschmann M, Hilaire G (2008) Oral treatment with desipramine improves breathing and life span in Rett syndrome mouse model. Respir Physiol Neurobiol 160(1):116–121
Zappella M, Genazzani A, Facchinetti F, Hayek G (1990) Bromocriptine in the Rett syndrome. Brain Dev 12(2):221–225
Zecca L, Bellei C, Costi P, Albertini A, Monzani E, Casella L, Gallorini M, Bergamaschi L, Moscatelli A, Turro NJ, Eisner M, Crippa PR, Ito S, Wakamatsu K, Bush WD, Ward WC, Simon JD, Zucca FA (2008) New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals. Proc Natl Acad Sci USA 105(45):17567–17572
Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, Chen WG, Lin Y, Savner E, Griffith EC, Hu L, Steen JA, Weitz CJ, Greenberg ME (2006) Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 52(2):255–269
Zoghbi HY, Percy AK, Glaze DG, Butler IJ, Riccardi VM (1985) Reduction of biogenic amine levels in the Rett syndrome. N Engl J Med 313(15):921–924
Zoghbi HY, Milstien S, Butler IJ, Smith EO, Kaufman S, Glaze DG, Percy AK (1989) Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome. Ann Neurol 25(1):56–60
Acknowledgments
This work is dedicated to the children and adults affected by Rett syndrome. We acknowledge support from the EuroRETT E-RARE network, Association Française du Syndrome de Rett (AFSR), the Agence Nationale de la Recherche (ANR), the Fondation Jérôme Lejeune and Inserm.
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Roux, JC., Villard, L. Biogenic Amines in Rett Syndrome: The Usual Suspects. Behav Genet 40, 59–75 (2010). https://doi.org/10.1007/s10519-009-9303-y
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DOI: https://doi.org/10.1007/s10519-009-9303-y