ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Pathophysiology of locus ceruleus neurons in a mouse model of Rett syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 128 citations in OpenAlex.
- Vagus Nerve Stimulation Paired With Tones Alters the Auditory Cortex Proteome in a Rat Model of Rett Syndrome.Developmental neurobiology · 2026Article
- Locus coeruleus α-synuclein overexpression induces prodromal Parkinsonian features in mice.NPJ Parkinson's disease · 2026Article
- Multidimensional Analysis of a Social Behavior Identifies Regression and Phenotypic Heterogeneity in a Female Mouse Model for Rett Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023Review
- Loss of mitochondrial enzyme GPT2 causes early neurodegeneration in locus coeruleus.Neurobiology of disease · 2022Article
- Breathing Abnormalities During Sleep and Wakefulness in Rett Syndrome: Clinical Relevance and Paradoxical Relationship With Circulating Pro-oxidant Markers.Frontiers in neurology · 2022Article
- Excitation and Inhibition Imbalance in Rett Syndrome.Frontiers in neuroscience · 2022Review
- Breathing disturbances in Rett syndrome.Handbook of clinical neurology · 2022Review
- A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels.Stem cell research & therapy · 2021Article
- Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer's disease.Scientific reports · 2021Article
- Clinical presentation of Rett syndrome in relation to quality of life and family functioning.The Journal of international medical research · 2021Article
- Restoration of motor learning in a mouse model of Rett syndrome following long-term treatment with a novel small-molecule activator of TrkB.Disease models & mechanisms · 2020Article
- The Pathophysiology of Rett Syndrome With a Focus on Breathing Dysfunctions.Physiology (Bethesda, Md.) · 2020Review
- The antitussive cloperastine improves breathing abnormalities in a Rett Syndrome mouse model by blocking presynaptic GIRK channels and enhancing GABA release.Neuropharmacology · 2020Article
- Sex differences in Mecp2-mutant Rett syndrome model mice and the impact of cellular mosaicism in phenotype development.Brain research · 2020Review
- Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome.International journal of molecular sciences · 2019Review
- Molecular Systems Biology of Neurodevelopmental Disorders, Rett Syndrome as an Archetype.Frontiers in integrative neuroscience · 2019Article
- Increasing Local Excitability of Brainstem Respiratory Nuclei Reveals a Distributed Network Underlying Respiratory Motor Pattern Formation.Frontiers in physiology · 2019Article
- Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.Current genomics · 2018Review
- Rett syndrome: insights into genetic, molecular and circuit mechanisms.Nature reviews. Neuroscience · 2018Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in the Methyl-CpG-binding protein-2 (MECP2) gene and is characterized by derangements in cognition, behavior, motor control, respiration and autonomic homeostasis, as well as seizures. Deficits in norepinephrine (NE) are thought to contribute to RTT pathogenesis, but little is known about how MeCP2 regulates function of noradrenergic neurons. We therefore characterized morphological, electrical, and neurochemical properties of neurons in the locus ceruleus (LC), the major source of noradrenergic innervation to the central neuraxis, in Mecp2 mutant mice. We found that MeCP2 null LC neurons are electrically hyperexcitable, smaller in size, and express less of the NE-synthesizing enzyme tyrosine hydroxylase (TH) compared with wild-type neurons. Increased excitability of mutant neurons is associated with reductions in passive membrane conductance and the amplitude of the slow afterhyperpolarization. Studies in Mecp2 heterozygotes, which are mosaic for the null allele, demonstrated that electrical hyperexcitability and reduced neuronal size are cell-autonomous consequences of MeCP2 loss, whereas reduced TH expression appears to reflect both cell-autonomous and non-autonomous influences. Finally, we found reduced levels of TH and norepinephrine in cingulate cortex, a forebrain target of the LC. Thus, genetic loss of MeCP2 results in a somewhat paradoxical LC neuron phenotype, characterized by both electrical hyperexcitability and reduced indices of noradrenergic function. Given the importance of the LC in modulating activity in brainstem and forebrain networks, we hypothesize that dysregulation of LC function in the absence of MeCP2 plays a key role in the pathophysiology of RTT.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.