Delayed Maturation of Neuronal Architecture and Synaptogenesis in Cerebral Cortex of Mecp2-Deficient Mice
Abstract
We detected morphologic abnormalities in the cerebral cortex of Mecp2-hemizygous (Mecp2(-/y)) mice. The cortical thickness of both somatosensory and motor cortices in mutants did not increase after 4 weeks of age, as compared with that in wild-type male mice. The density of neurons in those areas was significantly higher in layers II/III and V of Mecp2(-/y) mice than in wild-type mice, particularly in layers II/ III after 4 weeks of age. In layer II/III of the somatosensory cortex of Mecp2(-/y) mice, the diameter of the apical dendrite was thin and the number of dendritic spines was small. Electron microscopy revealed that two-week-old mutants already had numerous premature postsynaptic densities. These results indicate that Mecp2(-/y) mice suffered delayed neuronal maturation of the cerebral cortex and that the initial neuronal changes were caused by premature synaptogenesis. Rett syndrome patients with a heterozygous mutation of Mecp2 display developmental disorders including cortical malfunctions such as mental retardation, autism, and epilepsy. Our results provide evidence of the similarity with Rett syndrome brains in some respects and suggest that MeCP2/Mecp2 plays some role in synaptogenesis.
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Loss of MeCp2 results in reduced brain weight and thinning of the neocortex in some mouse models.
“Loss of MeCp2 results in reduced brain weight [67, 126], with thinning of the neocortex described in some mouse models [115, 200, 302].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [115]
These changes are apparently due to a delay in development and synapse formation in neurons resulting from Mecp2 haploinsufficiency, abnormalities that do not recover with age.
“These changes are apparently due to a delay in development and synapse formation in neurons resulting from Mecp2 haploinsufficiency [115, 330], which are abnormalities in development that do not recover with age.”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [115]
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- Authors
- Fukuda, T., Itoh, M., Ichikawa, T., Washiyama, K., & Goto, Y.-I.
- Affiliations
- National Center of Neurology and Psychiatry (JP)
- Brain Research Institute, Niigata University (JP)
- Corresponding author
- Itoh, Masayuki
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06
- Volume
- 64
- Issue
- 6
- Pages
- 537-544
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W46964427
- Cited by
- 221
- References
- 36
- Citations by year
- 2025: 13 · 2024: 10 · 2023: 3 · 2022: 16 · 2021: 16 · 2020: 11 · 2019: 9 · 2018: 11 · 2017: 12 · 2016: 17 · 2015: 13 · 2014: 12 · 2013: 7 · 2012: 16
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental 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
- MeCP2, MeCP2 deficiency, Rett syndrome, synaptogenesis, neuronal maturation, cerebral cortex, cortical thickness, somatosensory cortex, motor cortex, dendritic spines, postsynaptic density, neuronal density
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Cell Count, Cerebral Cortex, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Glial Fibrillary Acidic Protein, Immunohistochemistry, Male, Neurons, Parvalbumins, Repressor Proteins, Synapses, Silver Staining, Mice, Knockout, Gene Expression Regulation, Developmental, Microscopy, Electron, Transmission, Cell Size, Mice, Methyl-CpG-Binding Protein 2
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