miR-132/212 Modulates Seasonal Adaptation and Dendritic Morphology of the Central Circadian Clock

Cell Rep. 2017 Apr 18;19(3):505-520. doi: 10.1016/j.celrep.2017.03.057.

Abstract

The central circadian pacemaker, the suprachiasmatic nucleus (SCN), encodes day length information by mechanisms that are not well understood. Here, we report that genetic ablation of miR-132/212 alters entrainment to different day lengths and non-24 hr day-night cycles, as well as photoperiodic regulation of Period2 expression in the SCN. SCN neurons from miR-132/212-deficient mice have significantly reduced dendritic spine density, along with altered methyl CpG-binding protein (MeCP2) rhythms. In Syrian hamsters, a model seasonal rodent, day length regulates spine density on SCN neurons in a melatonin-independent manner, as well as expression of miR-132, miR-212, and their direct target, MeCP2. Genetic disruption of Mecp2 fully restores the level of dendritic spines of miR-132/212-deficient SCN neurons. Our results reveal that, by regulating the dendritic structure of SCN neurons through a MeCP2-dependent mechanism, miR-132/212 affects the capacity of the SCN to encode seasonal time.

Keywords: MeCP2; circadian rhythms; dendritic morphology; entrainment; miR-132/212; microRNA; seasonal timekeeping; spinogenesis; structural plasticity; suprachiasmatic nucleus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics*
  • Adaptation, Physiological / radiation effects
  • Animals
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Circadian Clocks / genetics*
  • Circadian Clocks / radiation effects
  • Dendrites / metabolism*
  • Dendrites / radiation effects
  • Dendritic Spines / metabolism
  • Dendritic Spines / radiation effects
  • Female
  • Gene Deletion
  • Gene Expression Regulation / radiation effects
  • Light
  • Male
  • Mesocricetus
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / metabolism
  • Photoperiod
  • Proteome / metabolism
  • Seasons*
  • Signal Transduction / radiation effects
  • Suprachiasmatic Nucleus / metabolism
  • Suprachiasmatic Nucleus / radiation effects
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • MIRN132 microRNA, mouse
  • MIRN212 microRNA, mouse
  • Methyl-CpG-Binding Protein 2
  • MicroRNAs
  • Proteome
  • TOR Serine-Threonine Kinases