ArticleHuman molecular genetics2019
Loss of MeCP2 in immature neurons leads to impaired network integration.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- High dopamine impairs early neuronal identity and morphology in human hippocampal progenitor cells.Frontiers in cell and developmental biology · 2026Article
- FMRP regulation of STAT3-MYC signaling is critical for adult hippocampal neurogenesis and cognitive flexibility.Cell death and differentiation · 2026Article
- Mecp2 deficiency impairs microscale cortical network topology and dynamics in a Rett syndrome mouse model.bioRxiv : the preprint server for biology · 2025Article
- Review
- MeCP2 Modulates Depression-Like Behaviors Comorbid to Chronic Pain by Regulating Adult Hippocampal Neurogenesis.CNS neuroscience & therapeutics · 2025Article
- Mitochondrial dysfunction and increased reactive oxygen species production in MECP2 mutant astrocytes and their impact on neurons.Scientific reports · 2024Article
- The selfish network: how the brain preserves behavioral function through shifts in neuronal network state.Trends in neurosciences · 2024Review
- TheThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Disruption of the autism gene and chromatin regulator KDM5A alters hippocampal cell identity.Science advances · 2023Article
- Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis.Hippocampus · 2023Review
- Re-formation of synaptic connectivity in dissociated human stem cell-derived retinal organoid cultures.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives.Frontiers in neuroscience · 2023Review
- Dysregulated cortical synaptic plasticity under methyl-CpG binding protein 2 deficiency and its implication in motor impairments.World journal of psychiatry · 2022Review
- Excitation and Inhibition Imbalance in Rett Syndrome.Frontiers in neuroscience · 2022Review
- Role of miR-132/methyl-CpG-binding protein 2 in the regulation of neural stem cell differentiation.Neural regeneration research · 2021Article
- Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction.Molecular autism · 2020Review
- Enriched environment ameliorates adult hippocampal neurogenesis deficits in Tcf4 haploinsufficient mice.BMC neuroscience · 2020Article
- Functional Network Mapping Reveals State-Dependent Response to IGF1 Treatment in Rett Syndrome.Brain sciences · 2020Article
- In vitro modeling of dendritic atrophy in Rett syndrome: determinants for phenotypic drug screening in neurodevelopmental disorders.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations or deletions in Methyl-CpG-binding Protein 2 (MeCP2), a brain-enriched transcriptional regulator. MeCP2 is highly expressed during neuronal maturation and its deficiency results in impaired dendritic morphogenesis and reduced dendritic spine numbers in developing neurons. However, whether MeCP2 deficiency impacts the integration of new neurons has not been directly assessed. In this study, we developed a modified rabies virus-mediated monosynaptic retrograde tracing method to interrogate presynaptic integration of MeCP2-deficient new neurons born in the adult hippocampus, a region with lifelong neurogenesis and plasticity. We found that selective deletion of MeCP2 in adult-born new neurons impaired their long-range connectivity to the cortex, whereas their connectivity within the local hippocampal circuits or with subcortical regions was not significantly affected. We further showed that knockdown of MeCP2 in primary hippocampal neurons also resulted in reduced network integration. Interestingly, (1-3) insulin-like growth factor-1 (IGF-1), a small peptide under clinical trial testing for RTT, rescued neuronal integration deficits of MeCP2-deficient neurons in vitro but not in vivo. In addition, (1-3) IGF-1 treatment corrected aberrant excitability and network synchrony of MeCP2-deficient hippocampal neurons. Our results indicate that MeCP2 is essential for immature neurons to establish appropriate network connectivity.
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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.