Screening of sleep assisting drug candidates with a Drosophila model

PLoS One. 2020 Jul 29;15(7):e0236318. doi: 10.1371/journal.pone.0236318. eCollection 2020.

Abstract

Lately, Drosophila has been favored as a model in sleep and circadian rhythm research due to its conserved mechanism and easily manageable operation. These studies have revealed the sophisticated parameters in whole-day sleep profiles of Drosophila, drawing connections between Drosophila sleep and human sleep. In this study, we tested several sleep deprivation protocols (mechanical shakes and light interruptions) on Drosophila and delineated their influences on Drosophila sleep. We applied a daytime light-deprivation protocol (DD) mimicking jet-lag to screen drugs that alleviate sleep deprivation. Characteristically, classical sleep-aid compounds exhibited different forms of influence: phenobarbital and pentobarbital modified total sleep time, while melatonin only shortened the latency to sleep. Such results construct the basis for further research on sleep benefits in other treatments in Drosophila. We screened seven herb extracts, and found very diverse results regarding their effect on sleep regulation. For instance, Panax notoginseng and Withania somnifera extracts displayed potent influence on total sleep time, while Melissa officinalis increased the number of sleep episodes. By comparing these treatments, we were able to rank drug potency in different aspects of sleep regulation. Notably, we also confirmed the presence of sleep difficulties in a Drosophila Alzheimer's disease (AD) model with an overexpression of human Abeta, and recognized clear differences between the portfolios of drug screening effects in AD flies and in the control group. Overall, potential drug candidates and receipts for sleep problems can be identified separately for normal and AD Drosophila populations, outlining Drosophila's potential in drug screening tests in other populations if combined with the use of other genetic disease tools.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / genetics
  • Animals
  • Circadian Rhythm / drug effects
  • Disease Models, Animal
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Gene Expression Regulation / genetics
  • Humans
  • Melatonin / pharmacology
  • Mutation
  • Panax notoginseng / chemistry
  • Phenobarbital / pharmacology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Sleep / drug effects
  • Sleep / genetics
  • Sleep / physiology*
  • Sleep Deprivation / drug therapy*
  • Sleep Deprivation / genetics
  • Sleep Deprivation / physiopathology
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / genetics
  • Sleep Wake Disorders / physiopathology
  • Withania / chemistry

Substances

  • Amyloid beta-Peptides
  • Plant Extracts
  • Melatonin
  • Phenobarbital

Grants and funding

YYW, WWM and IFP are full-time employees in Suzhou Joekai Biotechnology LLC (Joekai Biotech), Jiangsu, China. Joekai Biotech provided support in the form of salaries for authors [YYW, WWM, IFP], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. IFP and WWM also received Research Grants for International Collaborations (2017, 2018) from Science and Technology Bureau of Kunshan City.