title: Circadian rhythm of autophagy proteins in hippocampus is blunted by sleep fragmentation.
abstract: Autophagy is essential for normal cellular survival and activity. Circadian rhythms of autophagy have been studied in several peripheral organs but not yet reported in the brain. Here, we measured the circadian rhythm of autophagy-related proteins in mouse hippocampus and tested the effect of sleep fragmentation (SF). Expressions of the autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) and beclin were determined by western blotting and immunohistochemistry. Both the hippocampal LC3 signal and the ratio of its lipid-conjugated form LC3-II to its cytosolic form LC3-I showed a 24 h rhythm. The peak was seen at ZT6 (1 pm) and the nadir at ZT16 (1 am). The LC3 immunoreactivity in hippocampal CA1 pyramidal neurons also distributed differently, with more diffuse cytoplasmic appearance at ZT16. Chronic SF had a mild effect to disrupt the 24 h rhythm of LC3 and beclin expression. Interestingly, a greater effect of SF was seen after 24 h of recovery sleep when LC3-II expression was attenuated at both the peak and trough of circadian activities. Overall, the results show for the first time that the hippocampus has a distinct rhythm of autophagy that can be altered by SF.
authors.affiliation: a Biopotentials Sleep Center , Baton Rouge , LA , USA.|b Beijing Key Laboratory of Mental Disorders, Anding Hospital , Capitol Medical University , Beijing , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.affiliation: c Halberg Chronobiology Center , University of Minnesota , MN , USA.
authors.forename: Germaine G
authors.initials: GG
authors.lastname: Cornelissen-Guillaume
authors.affiliation: d Blood-Brain Barrier Group , Pennington Biomedical Research Center , Baton Rouge , LA , USA.
authors.forename: Junyun
authors.initials: J
authors.lastname: He
authors.affiliation: d Blood-Brain Barrier Group , Pennington Biomedical Research Center , Baton Rouge , LA , USA.
authors.forename: Abba J
authors.initials: AJ
authors.lastname: Kastin
authors.affiliation: d Blood-Brain Barrier Group , Pennington Biomedical Research Center , Baton Rouge , LA , USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Harrison
authors.affiliation: a Biopotentials Sleep Center , Baton Rouge , LA , USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins
keywords: Autophagy; circadian rhythm; hippocampus; sleep fragmentation