ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
A TrkB small molecule partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 149 citations in OpenAlex.
- BDNF in ventrolateral orbitofrontal cortex to dorsolateral striatum circuit moderates alcohol consumption, seeking and relapse.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Toward an NGF-based therapy for Rett syndrome.Frontiers in neuroscience · 2026Review
- Recent advances in epigenetic therapeutics for Rett syndrome: from mechanisms to clinical trials.Frontiers in behavioral neuroscience · 2026Review
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- MECP2 Dysfunction in Rett Syndrome: Molecular Mechanisms, Multisystem Pathology, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Small-Molecule Trk Agonists: Where Do We Go from Here?Journal of medicinal chemistry · 2025Review
- MeCP2 prevents against sustained ketamine-induced synaptic depression at inhibitory synapses.iScience · 2025Article
- Clinical-grade intranasal NGF fuels neurological and metabolic functions of Mecp2-deficient mice.Brain : a journal of neurology · 2025Article
- Rett Syndrome: Thinking Beyond Brain Borders.Advances in experimental medicine and biology · 2025Review
- Site-blocking antisense oligonucleotides as a mechanism to fine-tune MeCP2 expression.RNA (New York, N.Y.) · 2024Article
- GM1 Oligosaccharide Ameliorates Rett Syndrome Phenotypes In Vitro and In Vivo via Trk Receptor Activation.International journal of molecular sciences · 2024Article
- A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice.Disease models & mechanisms · 2024Article
- Development of Pleiotropic TrkB and 5-HTMolecules (Basel, Switzerland) · 2024Article
- Profile of Trofinetide in the Treatment of Rett Syndrome: Design, Development and Potential Place in Therapy.Drug design, development and therapy · 2024Review
- Adenosinergic System and BDNF Signaling Changes as a Cross-Sectional Feature of RTT: Characterization ofInternational journal of molecular sciences · 2023Article
- Mechanisms Controlling the Expression and Secretion of BDNF.Biomolecules · 2023Review
- C3-Symmetric Ligands in Drug Design: When the Target Controls the Aesthetics of the Drug.Molecules (Basel, Switzerland) · 2023Review
- Transgenic rodents as dynamic models for the study of respiratory rhythm generation and modulation: a scoping review and a bibliometric analysis.Frontiers in physiology · 2023Article
- Elp1 is required for development of visceral sensory peripheral and central circuitry.Disease models & mechanisms · 2022Article
- Chronic partial TrkB activation reduces seizures and mortality in a mouse model of Dravet syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Rett syndrome (RTT) results from loss-of-function mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2) and is characterized by abnormal motor, respiratory and autonomic control, cognitive impairment, autistic-like behaviors and increased risk of seizures. RTT patients and Mecp2-null mice exhibit reduced expression of brain-derived neurotrophic factor (BDNF), which has been linked in mice to increased respiratory frequency, a hallmark of RTT. The present study was undertaken to test the hypotheses that BDNF deficits in Mecp2 mutants are associated with reduced activation of the BDNF receptor, TrkB, and that pharmacologic activation of TrkB would improve respiratory function. We characterized BDNF protein expression, TrkB activation and respiration in heterozygous female Mecp2 mutant mice (Het), a model that recapitulates the somatic mosaicism for mutant MECP2 found in typical RTT patients, and evaluated the ability of a small molecule TrkB agonist, LM22A-4, to ameliorate biochemical and functional abnormalities in these animals. We found that Het mice exhibit (1) reduced BDNF expression and TrkB activation in the medulla and pons and (2) breathing dysfunction, characterized by increased frequency due to periods of tachypnea, and increased apneas, as in RTT patients. Treatment of Het mice with LM22A-4 for 4 weeks rescued wild-type levels of TrkB phosphorylation in the medulla and pons and restored wild-type breathing frequency. These data provide new insight into the role of BDNF signaling deficits in the pathophysiology of RTT and highlight TrkB as a possible therapeutic target in this disease.
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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.