Abstract
Rett syndrome (RTT) is an autism spectrum disorder with an incidence of ~1:10,000 females (reviewed in Bird, 2008; Chahrour et al., 2007; Francke, 2006). Affected
individuals are apparently normal at birth. Between 6–18 months of age, however, RTT patients begin to exhibit deceleration of head growth,
replacement of purposeful hand movements with stereotypic hand wringing, loss of speech,
social withdrawal and other autistic features. RTT is caused by loss of function mutations
in the gene that encodes methyl-CpG-binding protein 2 (Mecp2) (Amir et al., 1999),
a transcriptional repressor that targets genes essential for neuronal survival, dendritic
growth, synaptogenesis, and activity dependent plasticity. MECP2 is X-linked, and
males die soon after birth. Included in the RTT phenotype are cardiorespiratory disorders
involving the autonomic nervous system. The respiratory disorders, including the roles
of bioaminergic and brain derived neurotrophic factor (BDNF) signaling in the respiratory
pathophysiology of RTT have been recently reviewed (Bissonnette et al., 2007a; Ogier
et al., 2008; Katz et al., 2009). Here we will cover the work on RTT regarding respiration
that has appeared since 2009 as well as cardiovascular abnormalities.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Autonomic Neuroscience: Basic and ClinicalAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Correction of respiratory disorders in a mouse model of Rett syndrome.Proceedings of the National Academy of Sciences of the United States of America. 2010; 107: 18208-18213
- Cardiac disease and Rett syndrome.Archives of Disease in Childhood. 2006; 91: 440-443
- A novel hypomorphic MECP2 point mutation is associated with a neuropsychiatric phenotype.Human Genetics. 2009; 124: 615-623
- Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.Nature Genetics. 1999; 23: 185-188
- Central respiratory failure in a mouse model depends on the genetic background of the host.Advances in Experimental Medicine and Biology. 2010; 669: 21-24
- Neuropathology of Rett syndrome.Journal of Child Neurology. 2005; 20: 747-753
- Microscopic observations of the brain in Rett syndrome.Neuropediatrics. 1995; 26: 105-108
- The methyl-CpG-binding protein MeCP2 and neurological disease.Biochemical Society Transactions. 2008; 36: 575-583
- Possible role of bioaminergic systems in the respiratory disorders of Rett syndrome.in: Gaultier C. Genetic Basis for Respiratory Control Disorders. Springer US, New York2007: 271-289
- Autonomic cardiovascular control in methyl-CpG-binding protein 2 (Mecp2) deficient mice.Autonomic Neuroscience: Basic and Clinical. 2007; 136: 82-89
- The story of Rett syndrome: from clinic to neurobiology.Neuron. 2007; 56: 422-437
- Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes.Nature. 2010; 468: 263-269
- Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice.Nature Genetics. 2001; 27: 327-331
- Reversibility of functional deficits in experimental models of Rett syndrome.Biochemical Society Transactions. 2010; 38: 498-506
- Gene expression profiling in postmortem Rett Syndrome brain: differential gene expression and patient classification.Neurobiology of Disease. 2001; 8: 847-865
- Respiratory modulation of premotor cardiac vagal neurons in the brainstem.Respiratory Physiology & Neurobiology. 2010; 174: 102-110
- Differential distribution of the MeCP2 splice variants in the postnatal mouse brain.The Journal of Comparative Neurology. 2007; 501: 526-542
- Looking for inspiration: new perspectives on respiratory rhythm.Nature Reviews. 2006; 7: 232-242
- Mechanisms of disease: neurogenetics of MeCP2 deficiency.Nature Clinical Practice. 2006; 2: 212-221
- Survival with Rett syndrome: comparing Rett's original sample with data from the Australian Rett Syndrome Database.Developmental Medicine and Child Neurology. 2010; 52: 962-965
- Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2.Proceedings of the National Academy of Sciences of the United States of America. 2007; 104: 1931-1936
- Long QT syndrome.Journal of the American College of Cardiology. 2008; 51: 2291-2300
- Serotonergic modulation of the trigeminocardiac reflex neurotransmission to cardiac vagal neurons in the nucleus ambiguus.Journal of Neurophysiology. 2009; 102: 1443-1450
- Cardiac dysautonomia and serotonin plasma levels in Rett syndrome.Neuropediatrics. 2004; 35: 36-38
- A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome.Nature Genetics. 2001; 27: 322-326
- Reversal of neurological defects in a mouse model of Rett syndrome.Science (New York, N.Y). 2007; 315: 1143-1147
- MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212.Nature Neuroscience. 2010; 13: 1120-1127
- p.R270X MECP2 mutation and mortality in Rett syndrome.European Journal of Human Genetics. 2005; 13: 1235-1238
- Prolonged QT intervals and diminished heart rate variability in patients with Rett syndrome.Pacing & Clinical Electrophysiology. 1995; 18: 889
- Cerebellar gene expression profiles of mouse models for Rett syndrome reveal novel MeCP2 targets.BMC Medical Genetics. 2007; 8: 36
- Assessment of the maturity-related brainstem functions reveals the heterogeneous phenotypes and facilitates clinical management of Rett syndrome.Brain & Development. 2005; 27: S43-S53
- Functional evidence of brain stem immaturity in Rett syndrome.European Child & Adolescent Psychiatry. 1997; 6: 47-54
- Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder.Archives of Disease in Childhood. 2001; 85: 29-37
- Breathing disorders in Rett syndrome: progressive neurochemical dysfunction in the respiratory network after birth.Respiratory Physiology & Neurobiology. 2009; 168: 101-108
- Rett syndrome: analysis of deaths in the British survey.European Child & Adolescent Psychiatry. 1997; 6: 71-74
- Longevity in Rett syndrome: analysis of the North American Database.The Journal of Pediatrics. 2010; 156: e131
- Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA.Nature Neuroscience. 2007; 10: 1513-1514
- Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in Mecp2-null mice.Journal of Neuroscience. 2010; 30: 5303-5310
- The major form of MeCP2 has a novel N-terminus generated by alternative splicing.Nucleic Acids Research. 2004; 32: 1818-1823
- Chromosome 21-derived microRNAs provide an etiological basis for aberrant protein expression in human Down syndrome brains.The Journal of Biological Chemistry. 2010; 285: 1529-1543
- Rett syndrome in Australia: a review of the epidemiology.The Journal of Pediatrics. 2006; 148: 347-352
- Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex.Journal of Cerebral Blood Flow & Metabolism. 2009; 30: 744-756
- Serotonin targets inhibitory synapses to induce modulation of network functions.Philosophical Transactions of the Royal Society of London. 2009; 364: 2589-2602
- Early defects of GABAergic synapses in the brainstem of a MeCP2 mouse model of Rett syndrome.Journal of Neurophysiology. 2008; 99: 112-121
- A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome.Nature Genetics. 2004; 36: 339-341
- Breathing dysfunction in Rett syndrome: understanding epigenetic regulation of the respiratory network.Respiratory Physiology & Neurobiology. 2008; 164: 55-63
- Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome.Journal of Neuroscience. 2007; 27: 10912-10917
- Serotonin transporter abnormality in the dorsal motor nucleus of the vagus in Rett syndrome: potential implications for clinical autonomic dysfunction.Journal of Neuropathology and Experimental Neurology. 2005; 64: 1018-1027
- A working heart-brainstem preparation of the mouse.Journal of Neuroscience Methods. 1996; 65: 63-68
- Mecp2 deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice.Brain. 2006; 129: 887-898
- Determinants of inspiratory activity.Respiratory Physiology & Neurobiology. 2005; 147: 145-157
- The MECP2 duplication syndrome.American Journal of Medical Genetics. 2010; A 152A: 1079-1088
- Studying rhythmogenesis of breathing: comparison of in vivo and in vitro models.Trends in Neurosciences. 2001; 24: 464-472
- Disturbances in cardiorespiratory function during day and night in Rett syndrome.Pediatric Neurology. 2007; 37: 338-344
- Treatment with desipramine improves breathing and survival in a mouse model for Rett syndrome.The European Journal of Neuroscience. 2007; 25: 1915-1922
- BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses.Neuron. 1998; 21: 521-530
- A partial loss of function allele of methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome.Human Molecular Genetics. 2008; 17: 1718-1727
- Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities.Proceedings of the National Academy of Sciences of the United States of America. 2009; 106: 21966-21971
- Electrocardiographic findings in Rett syndrome: an explanation for sudden death?.The Journal of Pediatrics. 1994; 125: 80-82
- Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3.Neuron. 2002; 35: 243-254
- Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state.Molecular Cell. 2010; 37: 457-468
- Structural and functional architecture of respiratory networks in the mammalian brainstem.Philosophical Transactions of the Royal Society of London. 2009; 364: 2577-2587
- Hyperventilation in the awake state: potentially treatable component of Rett syndrome.Archives of Disease in Childhood. 1988; 63: 1039-1048
- Breathing dysfunctions associated with impaired control of postinspiratory activity in Mecp2−/y knockout mice.The Journal of Physiology. 2007; 579: 863-876
- Disturbances of breathing in Rett syndrome: results from patients and animal models.Advances in Experimental Medicine and Biology. 2008; 605: 503-507
- Spontaneous central apneas occur in the C57BL/6J mouse strain.Respiratory Physiology & Neurobiology. 2008; 160: 21-27
- Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function.Proceedings of the National Academy of Sciences of the United States of America. 2009; 106: 4882-4887
- Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain.Proceedings of the National Academy of Sciences of the United States of America. 2002; 99: 15536-15541
- Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice.Journal of Neuroscience. 2005; 25: 11521-11530
- A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis.Proceedings of the National Academy of Sciences of the United States of America. 2005; 102: 16426-16431
- Physiological definition of upper airway obstructions in mouse model for Rett syndrome.Respiratory Physiology & Neurobiology. 2010; 173: 146-156
- An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP.Proceedings of the National Academy of Sciences of the United States of America. 2008; 105: 9093-9098
- Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome.Pediatric Research. 2006; 60: 443-449
- Autonomic dysregulation in young girls with Rett Syndrome during nighttime in-home recordings.Pediatric Pulmonology. 2008; 43: 1045-1060
- Genome-wide analysis reveals methyl-CpG-binding protein 2-dependent regulation of microRNAs in a mouse model of Rett syndrome.Proceedings of the National Academy of Sciences of the United States of America. 2010; 107: 18161-18166
- Oral treatment with desipramine improves breathing and life span in Rett syndrome mouse model.Respiratory Physiology & Neurobiology. 2007; 160: 116-121
- Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation.Neuron. 2006; 52: 255-269
Article info
Publication history
Published online: February 14, 2011
Accepted:
January 18,
2011
Received in revised form:
January 12,
2011
Received:
October 21,
2010
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
