Hippocampal CA1 Pyramidal Neurons of Mecp2 Mutant Mice Show a Dendritic Spine Phenotype Only in the Presymptomatic Stage
Open accessAbstract
Alterations in dendritic spines have been documented in numerous neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, an X chromosome-linked disorder associated with mutations in MECP2, is the leading cause of intellectual disabilities in women. Neurons in Mecp2-deficient mice show lower dendritic spine density in several brain regions. To better understand the role of MeCP2 on excitatory spine synapses, we analyzed dendritic spines of CA1 pyramidal neurons in the hippocampus ofMecp2tm1.1Jaemale mutant mice by either confocal microscopy or electron microscopy (EM). At postnatal-day 7 (P7), well before the onset of RTT-like symptoms, CA1 pyramidal neurons from mutant mice showed lower dendritic spine density than those from wildtype littermates. On the other hand, at P15 or later showing characteristic RTT-like symptoms, dendritic spine density did not differ between mutant and wildtype neurons. Consistently, stereological analyses at the EM level revealed similar densities of asymmetric spine synapses in CA1 stratum radiatum of symptomatic mutant and wildtype littermates. These results raise caution regarding the use of dendritic spine density in hippocampal neurons as a phenotypic endpoint for the evaluation of therapeutic interventions in symptomatic Mecp2-deficient mice. However, they underscore the potential role of MeCP2 in the maintenance of excitatory spine synapses.
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Overall, studies in Mecp2 animal models indicate that neuronal and dendritic morphology changes may appear transiently during development or be variously affected, depending on developmental stage and MeCp2 gain- or loss-of-function.
“Overall, studies in the Mecp2 animal models indicate that neuronal and dendritic morphology changes may appear transiently during development or be variously affected, depending on developmental stage and MeCp2 gain- or loss-of-function [64, 180].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [64]
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- Authors
- Chapleau, C. A., Boggio, E. M., Calfa, G., Percy, A. K., Giustetto, M., & Pozzo-Miller, L.
- Affiliations
- Civitan International (US)
- Neuroscience Institute (IT)
- Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
- University of Turin (IT)
- Venue
- Neural Plasticity
- Publisher
- Wiley
- Published
- 2012
- Volume
- 2012
- Pages
- 1-9
- ISSN
- 1687-5443 (ISSN-L)
- 2090-5904
- PMC
- PMC3418521
- OpenAlex
- W2121919010
- Cited by
- 48
- References
- 35
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 7 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 2
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Neural Plasticity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Greater South Information System
- Funders
- National Institute of Neurological Disorders and Stroke (NS40593, NS057780, NS065027, IRSF0804, 2814, GGP09196)
- International Rett Syndrome Foundation (NS40593, NS057780, NS065027, IRSF0804, 2814, GGP09196)
- Italian Telethon Foundation (NS40593, NS057780, NS065027, IRSF0804, 2814, GGP09196)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- Rett syndrome, MeCP2, dendritic spine density, CA1 pyramidal neurons, hippocampus, presymptomatic stage, neurodevelopmental disorders
- MeSH terms
- Animals, Carbocyanines, Cell Count, Coloring Agents, Male, Mice, Inbred C57BL, Microscopy, Electron, Synapses, X Chromosome, Rett Syndrome, Pyramidal Cells, Mice, Knockout, Microscopy, Confocal, Endpoint Determination, Dendritic Spines, Mice, Methyl-CpG-Binding Protein 2, CA1 Region, Hippocampal
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