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Int J Mol Sci. 2017 Oct 26;18(11). pii: E2243. doi: 10.3390/ijms18112243.

Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging.

Author information

1
Department of Preclinical Research and Development, BioChron LLC, Worcester, MA 01605, USA. alexander.stank@gmail.com.
2
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA. alexander.stank@gmail.com.
3
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA. erinmcgowan20@gmail.com.
4
Department of Preclinical Research and Development, BioChron LLC, Worcester, MA 01605, USA. lilifish1964@gmail.com.
5
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA. lilifish1964@gmail.com.
6
Department of Preclinical Research and Development, BioChron LLC, Worcester, MA 01605, USA. irina.zhdanova@bio-chron.com.
7
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA. irina.zhdanova@bio-chron.com.

Abstract

Chronic high caloric intake (HCI) is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.

KEYWORDS:

anxiety; cell cycle; circadian; diurnal vertebrate; high caloric intake; neurogenesis; premature aging; scoliosis; sleep

PMID:
29072584
PMCID:
PMC5713213
DOI:
10.3390/ijms18112243
[Indexed for MEDLINE]
Free PMC Article

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