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. 2021 Dec;37(12):1713-1717.
doi: 10.1007/s12264-021-00746-0. Epub 2021 Jul 20.

Overexpression of MECP2 in the Suprachiasmatic Nucleus Alters Circadian Rhythm and Induces Abnormal Social Behaviors

Hailin Liu  1   2 , Zilong Qiu  3   4   5   6
Affiliations
Free PMC article

Overexpression of MECP2 in the Suprachiasmatic Nucleus Alters Circadian Rhythm and Induces Abnormal Social Behaviors

Hailin Liu et al. Neurosci Bull. 2021 Dec.
Free PMC article
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Circadian phenotypes of MECP2 transgenic mice and the regulation of circadian genes by MECP2 in the SCN. A Typical actograms showing wheel-running activity in constant darkness after LD entrainment. Red lines indicate the first day in constant darkness. B Graphs of innate periods of animals in constant darkness (n = 16 male MECP2-TG mice and n = 16 WT controls). C Actograms of jet-lag experiments in which male MECP2-TG mice (n = 8) and WT controls (n = 9) were subjected to an 8-h phase advance. Red lines indicate the start of the new LD cycle. D Group analysis of re-entrainment. E–G Typical immunohistochemical staining for MECP2, BMAL1, and PER2 proteins in the SCN (scale bar, 100 μm) H–J Relative signal intensities of MECP2, BMAL1, and PER2 proteins in the SCN. K–M Quantitative real-time PCR analysis of MECP2, Bmal1, and Per2 mRNA in the SCN. N Quantitative real-time PCR analysis of mir-142-3p mRNA in the hypothalamus. Mice in E–N were on the FVB background and sacrificed at ZT10 (n ≥3 mice per genotype). Values in B, D, and H–N represent the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; two-tailed t-test.
Fig. 2
Fig. 2
Restoration of normal MeCP2 levels in the SCN rescues the circadian defect and social recognition deficit in adult MECP2 transgenic mice, and overexpression of MECP2 in the SCN is sufficient to induce an abnormal circadian rhythm and social behaviors in adult WT mice. A Representative images of HA-SaCas9 expression in a rescued mouse. B Typical actograms showing wheel-running activity in constant darkness after LD entrainment. Red lines indicate the first day in constant darkness. C Normalizing the MeCP2 levels in the SCN of MECP2-TG mice rescues the innate period of animals in constant darkness. Results from MECP2-TG males (n = 10 mice) injected with sghMECP2 virus, MECP2-TG males (n = 5 mice) injected with control virus, and WT males (n = 5) injected with control virus. D, E Normalizing the MeCP2 levels in the SCN of MECP2-TG mice rescues impaired social recognition behavior in the three-chamber test (n = 5 for WT-CTL and MECP2-TG-CTL, n = 10 for MECP2-TG-Normalized). Time is defined as the amount of time the mouse spends in a rectangular area 7 cm from the length and width of the sides of the cage. F Representative images of HA-MECP2 expression in an MECP2-OE mouse. G Typical actograms showing wheel-running activity in constant darkness after LD entrainment. Red lines indicate the first day in constant darkness. H Overexpression of MECP2 in the SCN is sufficient to induce an abnormal circadian rhythm (n = 7 for WT-CTL and n = 5 for MECP2-OE). I The activity level of MECP2-OE mice is significantly lower than that of WT-CTL mice (n = 7 for WT-CTL and n = 5 for MECP2-OE). J–L Overexpression of MECP2 in the SCN is sufficient to induce abnormal social behaviors (n = 7 for WT-CTL and n = 5 for MECP2-OE). The definition of time is the same as in D and E. Values in C–E and H–I represent the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001; ns, not significant; two-tailed t-test in C, H, and I, two-tailed paired t-test in D, E, and J–L.
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References

    1. Carmassi C, Palagini L, Caruso D, Masci I, Nobili L, Vita A, et al. Systematic review of sleep disturbances and circadian sleep desynchronization in autism spectrum disorder: Toward an integrative model of a self-reinforcing loop. Front Psychiatry. 2019;10:366. doi: 10.3389/fpsyt.2019.00366. - DOI - PMC - PubMed
    1. Pinato L, Galina Spilla CS, Markus RP, da Silveira Cruz-Machado S. Dysregulation of circadian rhythms in autism spectrum disorders. Curr Pharm Des. 2019;25:4379–4393. doi: 10.2174/1381612825666191102170450. - DOI - PubMed
    1. Ramocki MB, Peters SU, Tavyev YJ, Zhang F, Carvalho CM, Schaaf CP, et al. Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome. Ann Neurol. 2009;66:771–782. doi: 10.1002/ana.21715. - DOI - PMC - PubMed
    1. Ramocki MB, Tavyev YJ, Peters SU. The MECP2 duplication syndrome. Am J Med Genet A. 2010;152A:1079–1088. doi: 10.1002/ajmg.a.33184. - DOI - PMC - PubMed
    1. Sandweiss AJ, Brandt VL, Zoghbi HY. Advances in understanding of Rett syndrome and MECP2 duplication syndrome: prospects for future therapies. Lancet Neurol. 2020;19:689–698. doi: 10.1016/S1474-4422(20)30217-9. - DOI - PubMed

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