ArticleJournal of applied physiology (Bethesda, Md. : 1985)2013
A selective 5-HT1a receptor agonist improves respiration in a mouse model of Rett syndrome.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- MECP2 Dysfunction in Rett Syndrome: Molecular Mechanisms, Multisystem Pathology, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Review
- Rett Syndrome: The Emerging Landscape of Treatment Strategies.CNS drugs · 2024Review
- Impact of Serotonergic 5HTInternational journal of molecular sciences · 2024Article
- Revisiting the Role of Serotonin in Sleep-Disordered Breathing.International journal of molecular sciences · 2024Review
- Exploring the role of the Kölliker-Fuse nucleus in breathing variability by mathematical modelling.The Journal of physiology · 2024Article
- Drug repurposing in Rett and Rett-like syndromes: a promising yet underrated opportunity?Frontiers in medicine · 2024Article
- Inhibitory synaptic transmission is impaired in the Kölliker-Fuse of male, but not female, Rett syndrome mice.Journal of neurophysiology · 2023Article
- 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
- 5-HTInternational journal of molecular sciences · 2022Article
- Breathing disturbances in Rett syndrome.Handbook of clinical neurology · 2022Review
- Aberrant lung lipids cause respiratory impairment in a Mecp2-deficient mouse model of Rett syndrome.Human molecular genetics · 2021Article
- Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin.Scientific reports · 2021Article
- Modulation of Serotonin Receptors in Neurodevelopmental Disorders: Focus on 5-HT7 Receptor.Molecules (Basel, Switzerland) · 2021Review
- Neurochemistry of the Kölliker-Fuse nucleus from a respiratory perspective.Journal of neurochemistry · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- The antitussive cloperastine improves breathing abnormalities in a Rett Syndrome mouse model by blocking presynaptic GIRK channels and enhancing GABA release.Neuropharmacology · 2020Article
- Drug Studies on Rett Syndrome: From Bench to Bedside.Journal of autism and developmental disorders · 2020Review
- Morphine-induced respiratory depression is independent of β-arrestin2 signalling.British journal of pharmacology · 2020Article
- Differential impact of two critical respiratory centres in opioid-induced respiratory depression in awake mice.The Journal of physiology · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Rett syndrome is a neurological disorder caused by loss of function mutations in the gene that encodes the DNA binding protein methyl-CpG-binding protein 2 (Mecp2). A prominent feature of the syndrome is disturbances in respiration characterized by frequent apnea and an irregular interbreath cycle. 8-Hydroxy-2-dipropylaminotetralin has been shown to positively modulate these disturbances (Abdala AP, Dutschmann M, Bissonnette JM, Paton JF, Proc Natl Acad Sci U S A 107: 18208-18213, 2010), but the mode of action is not understood. Here we show that the selective 5-HT1a biased agonist 3-chloro-4-fluorophenyl-(4-fluoro-4-{[(5-methylpyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone (F15599) decreases apnea and corrects irregularity in both heterozygous Mecp2-deficient female and in Mecp2 null male mice. In whole cell voltage-clamp recordings from dorsal raphe neurons, F15599 potently induced an outward current, which was blocked by barium, reversed at the potassium equilibrium potential, and was antagonized by the 5-HT1a antagonist WAY100135. This is consistent with somatodendritic 5-HT1a receptor-mediated activation of G protein-coupled inwardly rectifying potassium channels (GIRK). In contrast, F15599 did not activate 5-HT1b/d receptors that mediate inhibition of glutamate release from terminals in the nucleus accumbens by a presynaptic mechanism. Thus F15599 activated somatodendritic 5-HT1a autoreceptors, but not axonal 5-HT1b/d receptors. In unanesthetized Mecp2-deficient heterozygous female mice, F15599 reduced apnea in a dose-dependent manner with maximal effect of 74.5 ± 6.9% at 0.1 mg/kg and improved breath irrregularity. Similarly, in Mecp2 null male mice, apnea was reduced by 62 ± 6.6% at 0.25 mg/kg, and breathing became regular. The results indicate respiration is improved with a 5-HT1a agonist that activates GIRK channels without affecting neurotransmitter release.
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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.