Reversal of Social Recognition Deficit in Adult Mice with MECP2 Duplication via Normalization of MeCP2 in the Medial Prefrontal Cortex
Open accessAbstract
Methyl-CpG binding protein 2 (MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing. Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, heightened anxiety, epilepsy, autistic phenotypes, and early death. Reversal of the abnormal phenotypes in adult mice with MECP2 duplication (MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated. However, whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown. Here, we found that MECP2-TG mice showed a significant social recognition deficit, and were prone to display aversive-like behaviors, including heightened anxiety-like behaviors and a fear generalization phenotype. In addition, reduced locomotor activity was observed in MECP2-TG mice. However, appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice. Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors. We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex (mPFC) and bed nuclei of the stria terminalis (BST) of adult MECP2-TG mice, and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit. These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice, and provide new insight into potential therapies for MECP2 duplication syndrome.
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Restoring Mecp2 levels within the PFC in mice via CRISPR-Cas9 or DREADDS can restore some endophenotypes such as social recognition deficits or long-term retrieval of auditory conditioned fear.
“Restoring Mecp2 levels within the PFC in mice via state-of-the-art techniques such as CRISPR-Cas9 or DREADDS can restore some of the endophenotypes such as social recognition deficits or long-term retrieval of auditory conditioned fear [267, 270, 271].”
From Development of prefrontal cortex (2022) · cites this paper as [271]
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Self-citationInhibitory inputs from hippocampal CA1 to retrosplenial agranular cortex gate social behaviorPreprint
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Neurobiological mechanisms of social recognition memory
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Gut microbiota-derived 5-HTP penetrates the host blood–brain barrier and ameliorates autism symptoms
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- Authors
- Yu, B., Yuan, B., Dai, J.-K., Cheng, T.-L., Xia, S.-N., He, L.-J., Yuan, Y.-T., Zhang, Y.-F., Xu, H.-T., Xu, F.-Q., Liang, Z.-F., & Qiu, Z.-L.
- Affiliations
- Chinese Academy of Sciences (CN)
- Howard Hughes Medical Institute (US)
- Venue
- Neuroscience Bulletin
- Published
- 2020-03-07
- Volume
- 36
- Issue
- 6
- Pages
- 570-584
- ISSN
- 1995-8218 (ISSN-L)
- 1673-7067
- PMC
- PMC7271088
- OpenAlex
- W3009313600
- Cited by
- 58
- References
- 40
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 4 · 2022: 18 · 2021: 10 · 2020: 6
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience Bulletin (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- MECP2 duplication syndrome, MeCP2, medial prefrontal cortex, anxiety-like behavior, fear generalization, locomotor activity, CRISPR/Cas9 genome editing, transgenic mice, neurodevelopmental disorders, social behavior
- MeSH terms
- Animals, Anxiety, China, Disease Models, Animal, Fear, Male, Mice, Transgenic, Social Behavior, Prefrontal Cortex, Gene Duplication, Recognition, Psychology, Mice, Methyl-CpG-Binding Protein 2
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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