Widespread changes in dendritic and axonal morphology in Mecp2‐mutant mouse models of rett syndrome: Evidence for disruption of neuronal networks
Abstract
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X‐linked gene MECP2. Girls with RTT show dramatic changes in brain function, but relatively few studies have explored the structure of neural circuits. Examining two mouse models of RTT (Mecp2B and Mecp2J), we previously documented changes in brain anatomy. Herein, we use confocal microscopy to study the effects of MeCP2 deficiency on the morphology of dendrites and axons in the fascia dentata (FD), CA1 area of hippocampus, and motor cortex following Lucifer yellow microinjection or carbocyanine dye tracing. At 3 weeks of age, most (33 of 41) morphological parameters were significantly altered in Mecp2B mice; fewer (23 of 39) were abnormal in Mecp2J mice. There were striking changes in the density and size of the dendritic spines and density and orientation of axons. In Mecp2B mice, dendritic spine density was decreased in the FD (∼11%), CA1 (14–22%), and motor cortex (∼16%). A decreased spine head size (∼9%) and an increased spine neck length (∼12%) were found in Mecp2B FD. In addition, axons in the motor cortex were disorganized. In Mecp2J mice, spine density was significantly decreased in CA1 (14–26%). In both models, dendritic swelling and elongated spine necks were seen in all areas studied. Marked variation in the type and extent of changes was noted in dendrites of adjacent neurons. Electron microscopy confirmed abnormalities in dendrites and axons and showed abnormal mitochondria. Our findings document widespread abnormalities of dendrites and axons that recapitulate those seen in RTT. J. Comp. Neurol. 514:240–258, 2009. © 2009 Wiley‐Liss, Inc.
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When monocular deprivation was performed from postnatal day 26 to postnatal day 31-33, MeCP2-deficient primary visual cortex did not show ocular dominance plasticity.
“When MD was performed from P26 to P31-P33, WT V1 showed OD plasticity (Left), whereas MeCP2 -/y V1 did not (77).”
From MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex (2015) · cites this paper as [77]
When monocular deprivation was performed from postnatal day 26 to postnatal day 31-33, wild-type primary visual cortex showed ocular dominance plasticity.
“When MD was performed from P26 to P31-P33, WT V1 showed OD plasticity (Left), whereas MeCP2 -/y V1 did not (77).”
From MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex (2015) · cites this paper as [77]
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“Indeed, RTT neurons show smaller soma and reduced dendritic arborisation compared to healthy neurons (Belichenko et al., 2009; Fukuda et al., 2005; Jentarra et al., 2010; Perego et al., 2022).”
- Authors
- Belichenko, P. V., Wright, E. E., Belichenko, N. P., Masliah, E., Li, H. H., Mobley, W. C., & Francke, U.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- University of California San Diego (US)
- Corresponding author
- Belichenko, Pavel V.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2009-04-02
- Volume
- 514
- Issue
- 3
- Pages
- 240-258
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2045042214
- Cited by
- 272
- References
- 58
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 19 · 2023: 16 · 2022: 12 · 2021: 13 · 2020: 11 · 2019: 6 · 2018: 12 · 2017: 26 · 2016: 17 · 2015: 18 · 2014: 27 · 2013: 14 · 2012: 27
- FWCI
- 12.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Rett syndrome, MeCP2, dendritic spine density, dendritic morphology, axon morphology, dentate gyrus, hippocampal CA1, motor cortex, mitochondrial abnormalities, dendritic swelling
- MeSH terms
- Analysis of Variance, Animals, Axons, Carbocyanines, Disease Models, Animal, Hippocampus, Isoquinolines, Male, Mice, Transgenic, Microinjections, Microscopy, Electron, Motor Cortex, Neurons, Rett Syndrome, Microscopy, Confocal, Dendritic Spines, Mice, Methyl-CpG-Binding Protein 2
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