Mecp2 organizes juvenile social behavior in a sex-specific manner
Open accessAbstract
Methyl-CpG-binding protein 2 (MeCP2) binds methylated DNA and recruits corepressor proteins to modify chromatin and alter gene transcription. Mutations of the MECP2 gene can cause Rett syndrome, whereas subtle reductions of MeCP2 expression may be associated with male-dominated social and neurodevelopmental disorders. We report that transiently decreased amygdala Mecp2 expression during a sensitive period of brain sexual differentiation disrupts the organization of sex differences in juvenile social play behavior. Interestingly, neonatal treatment with Mecp2 small interfering RNA within the developing amygdala reduced juvenile social play behavior in males but not females. Reduced Mecp2 expression did not change juvenile sociability or anxiety-like behavior, suggesting that this disruption is associated with subtle behavioral modification. This suggests that Mecp2 may have an overlooked role in the organization of sexually dimorphic behaviors and that male juvenile behavior is particularly sensitive to Mecp2 disruption during this period of development.
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AVP may act via other nuclei not considered in the present study that likely contribute to AVP's actions on play.
“AVP may act via other nuclei not considered in the present study that likely contribute to AVP’s actions on play, e.g., nucleus circularis, supraoptic nucleus, medial amygdaloid nucleus (Cheng et al., 2008; Kurian et al., 2008; Forbes-Lorman et al., 2012).”
From Sexually dimorphic role for vasopressin in the development of social play (2014) · cites this paper as Kurian et al., 2008
The Results section reports that disrupting Mecp2 in the developing amygdala reduced juvenile social play in male rats, supporting a role for the amygdala in play. The paper does not identify the medial amygdaloid nucleus specifically or address AVP acting through it, the nucleus circularis, or the supraoptic nucleus (searched: AVP, vasopressin, and the named nuclei). No page numbers are available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSilencing MeCP2 expression in the MeA reduced social play and AVP mRNA expression in the MeA in males but not females.
“Likewise, silencing MeCP2 expression in the MeA reduced social play (Kurian et al., 2008) as well as AVP mRNA expression in the MeA (Forbes-Lorman et al., 2012) in males but not in females.”
From Sex-specific modulation of juvenile social play by vasopressin (2013) · cites this paper as Kurian et al., 2008
The Results section reports that neonatal Mecp2 siRNA treatment in the developing amygdala reduced juvenile social play in male rats but not females. The paper describes amygdala targeting, not specifically the medial amygdala (MeA). AVP mRNA expression is attributed to the separate Forbes-Lorman et al. citation, so it is not judged against Kurian et al. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe amount of MeCP2 siRNA used induced a transient and localized reduction in MeCP2 expression within the amygdala.
“We have previously shown that this amount of MeCP2 siRNA induced a transient and localized reduction in MeCP2 expression within the amygdala.14”
From Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression (2012) · cites this paper as [14]
MeCP2 siRNA infusion into the amygdala does not reduce MeCP2 levels in the hypothalamus.
“we have previously confirmed that the MeCP2 siRNA infusion into the amygdala does not reduce MeCP2 levels in the hypothalamus.14”
From Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression (2012) · cites this paper as [14]
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References 30 · Cited by 100
Research works printed but not linked: 25
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- Authors
- Kurian, J. R., Bychowski, M. E., Forbes-Lorman, R. M., Auger, C. J., & Auger, A. P.
- Affiliations
- University of Wisconsin–Madison (US)
- ORCID
- Auger, Anthony P.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-07-09
- Volume
- 28
- Issue
- 28
- Pages
- 7137-7142
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2569867
- OpenAlex
- W2076173286
- Cited by
- 100
- References
- 30
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 12 · 2015: 8 · 2014: 6 · 2013: 13 · 2012: 6
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH072956, T32 MH75880, T32MH075880)
- 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 › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- MeCP2, Rett syndrome, sex differences, amygdala, sexual differentiation of the brain, sensitive period, siRNA knockdown, anxiety-like behavior, chromatin modification, gene expression
- MeSH terms
- Adaptation, Ocular, Amygdala, Analysis of Variance, Animals, Animals, Newborn, Anxiety, Behavior, Animal, Exploratory Behavior, Female, Male, Pregnancy, Sexual Behavior, Animal, Sex Characteristics, Social Behavior, Gene Expression Regulation, Developmental, Maze Learning, RNA, Small Interfering, Rats, Methyl-CpG-Binding Protein 2
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