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Phenotypic consequences of genetic deletion of the glial circadian clock Bmal1 in mice
Author(s) -
Kofuji Paulo,
Massman Logan,
Engeland William
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1010.14
Subject(s) - per2 , circadian rhythm , biology , circadian clock , clock , suprachiasmatic nucleus , microbiology and biotechnology , hypothalamus , endocrinology , light effects on circadian rhythm , medicine , neuroscience
Glial cells have emerged as key players in brain information processing given the extensive neuronal‐glial and glial‐neuronal communication that takes place at synapses in the central nervous system. Glial cells also express an intrinsic molecular clock and release the neuromodulator ATP in a circadian fashion. Also disruption of glial signaling in fruit flies severely disrupts behavioral circadian rhythms. Collectively, these data suggest that glial cells and their intrinsic circadian rhythms have an important role in modulating circadian rhythmicity. In an effort to link glial cell‐specific circadian clocks to organismal circadian rhythmicity, we studied mice in which the canonical clock gene Aryl hydrocarbon receptor nuclear translocator‐like protein 1 ( Bmal1 ) is selectively disrupted in astrocytes (GFAP‐Bmal1‐cKO ). Staining of brain sections for BMAL1 reveals loss of expression in astrocytes, but not in neurons. By crossing GFAP‐Bmal1‐cKO mice with the Per2 Luc knock‐in mice in which the clock gene Per2 is fused with the reporter gene Luciferase, we performed real time luminescence analysis of Per2 gene expression from cultured astrocytes and explant tissues. Cultured astrocytes from GFAP‐Bmal1‐cKO / Per2 Luc mice show reduced PER2 Luc rhythmicity in comparison with control cultured astrocytes. Ex vivo explants from GFAP‐Bmal1‐cKO / Per2 Luc mice of the suprachiasmatic nucleus, adrenal gland, cornea, lung, liver, and pituitary exhibited robust circadian rhythms of PER2 Luc rhythmicity. Running wheel activity from GFAP‐Bmal1‐cKO mice subjected to a 12:12h light‐dark cycle reveals locomotor activity that was largely indistinguishable from wild‐type controls. In constant darkness, some mutant mice exhibited faster free running periods. Finally, some mutant mice also exhibited abnormal entrainment to a skeleton photoperiod. These experiments suggest an important role of the intrinsic circadian clock in glial cells for behavioral rhythmicity. Support or Funding Information RO3 NS3NS094419