Daily Rhythmic Behaviors and Thermoregulatory Patterns Are Disrupted in Adult Female MeCP2-Deficient Mice

Division of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
PLoS ONE (Impact Factor: 3.53). 04/2012; 7(4):e35396. DOI: 10.1371/journal.pone.0035396
Source: PubMed

ABSTRACT Mutations in the X-linked gene encoding Methyl-CpG-binding protein 2 (MECP2) have been associated with neurodevelopmental and neuropsychiatric disorders including Rett Syndrome, X-linked mental retardation syndrome, severe neonatal encephalopathy, and Angelman syndrome. Although alterations in the performance of MeCP2-deficient mice in specific behavioral tasks have been documented, it remains unclear whether or not MeCP2 dysfunction affects patterns of periodic behavioral and electroencephalographic (EEG) activity. The aim of the current study was therefore to determine whether a deficiency in MeCP2 is sufficient to alter the normal daily rhythmic patterns of core body temperature, gross motor activity and cortical delta power. To address this, we monitored individual wild-type and MeCP2-deficient mice in their home cage environment via telemetric recording over 24 hour cycles. Our results show that the normal daily rhythmic behavioral patterning of cortical delta wave activity, core body temperature and mobility are disrupted in one-year old female MeCP2-deficient mice. Moreover, female MeCP2-deficient mice display diminished overall motor activity, lower average core body temperature, and significantly greater body temperature fluctuation than wild-type mice in their home-cage environment. Finally, we show that the epileptiform discharge activity in female MeCP2-deficient mice is more predominant during times of behavioral activity compared to inactivity. Collectively, these results indicate that MeCP2 deficiency is sufficient to disrupt the normal patterning of daily biological rhythmic activities.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Iindex of published papers on thermology or temperature measurement Voluime 4: 2011 to 2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Disturbances in the sleep/wake cycle are prevalent in patients with Rett Syndrome (RTT). We sought to determine whether the circadian system is disrupted in a RTT model, Mecp2(-/y) mice. We found that MeCP2 mutants showed decreased strength and precision of daily rhythms of activity coupled with extremely fragmented sleep. The central circadian clock (suprachiasmatic nucleus) exhibited significant reduction in the number of neurons expressing vasoactive intestinal peptide (VIP) as well as compromised spontaneous neural activity. The molecular clockwork was disrupted both centrally in the SCN and in peripheral organs, indicating a general disorganization of the circadian system. Disruption of the molecular clockwork was observed in fibroblasts of RTT patients. Finally, MeCP2 mutant mice were vulnerable to circadian disruption as chronic jet lag accelerated mortality. Our findings suggest an integral role for MeCP2 in the circadian timing system, provides a possible mechanistic explanation for the sleep/wake disturbances observed in RTT patients. The work raises the possibility that RTT patients may benefit from a temporally structured environment. Copyright © 2015. Published by Elsevier Inc.
    Neurobiology of Disease 03/2015; 77. DOI:10.1016/j.nbd.2015.03.009 · 5.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in the X-linked gene encoding methyl CpG-binding protein 2 (MeCP2) have been linked to a neurodevelopmental disorder known as Rett syndrome. The disorder is associated with a number of symptoms, of which epileptic seizures are common. In this study we examined the presence of high frequency oscillations (HFOs) and their interactions with low frequency oscillations (LFOs) during epileptiform-like discharges using intracranial electroencephalogram (iEEG) recordings from male and female Mecp2-deficient mice. The study compared differences in mean HFO power levels normalized to baseline along with LFO-HFO modulation observed in short and long duration discharges. Short duration discharges, common to both male and female Mecp2-deficient mice, showed a decrease in mean HFO power levels compared to baseline levels. During the short duration discharges the theta (7-9 Hz) LFOs were found to modulate fast ripple (350-500 Hz) HFOs predominantly in the female Mecp2-deficient mice. Long duration discharges, predominantly observed in male Mecp2-deficient mice, were found to have elevated mean power levels in the ripple (80-200 Hz) and fast ripple (350-500 Hz) frequency ranges when compared to baseline. During the long duration discharges a lower frequency range theta LFO (4-6 Hz) modulated both the ripple (80-200 Hz) and fast ripple (350-500 Hz) HFOs. These findings suggest that the long duration discharges observed in male Mecp2-deficient mice share biomarkers indicative of seizure-like activity.

Full-text (3 Sources)

Available from
May 20, 2014