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Joan C Hendricks

Publications and source records attributed to Joan C Hendricks.

8 recordsLinked to original sources

A Drosophila model for age-associated changes in sleep:wake cycles.

One of the most consistent behavioral changes that occurs with age in humans is the loss of sleep consolidation. This can be quite disruptive and yet little is known about its underlying basis. To better understand the effects of aging on sleep:wake cycles, we sought to study this problem in Drosophila melanogaster, a powerful system for research on aging and behavior. By assaying flies of different ages as well as monitoring individual flies constantly over the course of their lifetime, we found that the strength of sleep:wake cycles decreased and that sleep became more fragmented with age in Drosophila. These changes in sleep:wake cycles became faster or slower with manipulations of ambient temperature that decreased or increased lifespan, respectively, demonstrating that they are a function of physiological rather than chronological age. The effect of temperature on lifespan was not mediated by changes in overall activity level or sleep amount. Flies treated with the oxidative stress-producing reagent paraquat showed a breakdown of sleep:wake cycles similar to that seen with aging, leading us to propose that the accumulation of oxidative damage with age contributes to the changes in rhythm and sleep. Together, these findings establish Drosophila as a valuable model for studying age-associated sleep fragmentation and breakdown of rhythm strength, and indicate that these changes in sleep:wake cycles are an integral part of the physiological aging process.

Aging↗

Why a fly? Using Drosophila to understand the genetics of circadian rhythms and sleep.

Among simple model systems, Drosophila has specific advantages for neurobehavioral investigations. It has been particularly useful for understanding the molecular basis of circadian rhythms. In addition, the genetics of fruit-fly sleep are beginning to develop. This review summarizes the current state of understanding of circadian rhythms and sleep in the fruit fly for the readers of Sleep. We note where information is available in mammals, for comparison with findings in fruit flies, to provide an evolutionary perspective, and we focus on recent findings and new questions. We propose that sleep-specific neural activity may alter cellular function and thus accomplish the restorative function or functions of sleep. In conclusion, we sound some cautionary notes about some of the complexities of working with this "simple" organism.

Animals↗

Modafinil maintains waking in the fruit fly drosophila melanogaster.

Fruit flies exhibit a sleep-like rest state that shares behavioral characteristics with mammalian sleep, including a homeostatic increase in rest after deprivation by mechanical methods. We tested the effect of modafinil, a novel wake-promoting agent, to discover whether its effect is conserved. Flies fed various concentrations of modafinil were compared to groups of control flies fed diluent only. Flies were also tested for a homeostatic response to the modafinil-related rest deprivation by examining rest and activity during recovery after 48H modafinil administration, compared to rest deprivation alone and to both treatments combined. The duration and consolidation of rest, and the duration, intensity, and circadian rhythms of activity were measured. Modafinil significantly and dose-dependently decreased rest when fed at concentrations from 2.5 mg/ml to 0.3125 mg/ml. Activity intensity was not increased, and circadian timing was unchanged, although the 2.5 mg/ml dose blunted the amplitude of overt circadian locomotor rhythms. Compared to controls, the duration of rest bouts was decreased in flies fed 2.5 mg/ml, and waking was frequently interrupted by 5-min periods of immobility. A rest rebound (significant increase in rest) followed withdrawal of either 2.5mg/ml or 0.625mg/ml modafinil after 48H. When directly compared to 6H total rest deprivation, the increase after withdrawal was briefer, reminiscent of the attenuated rest rebound seen in mammals, including humans, after modafinil. However, modafinil withdrawal combined with 6H total rest deprivation significantly enhanced the rebound, suggesting that a rest debt is accumulating during modafinil. We conclude that modafinil affects states of arousal in Drosophila in the same direction as it does in mammals. This discovery provides a tool for searching for conserved molecular mechanisms by which modafinil regulates rest and waking.

Animals↗

Invited review: Sleeping flies don't lie: the use of Drosophila melanogaster to study sleep and circadian rhythms.

During the past century, flies thoroughly proved their value as an animal model for the study of the genetics of development and basic cell processes. During the past three decades, they have also been extensively used to study the genetics of behavior. For both circadian rhythms and for sleep, flies are helping us to understand the genetic mechanisms that underlie these complex behaviors. Since 1971, discoveries in the fly have led the way to a number of significant discoveries, establishing a mechanistic framework that is now known to be conserved in the mammalian clock. The highlights of this history are described. For sleep, the use of the fly as a model is relatively new, that is, only within the past 2 yr. Nonetheless, studies have already established that two transcription factors alter rest and rest homeostasis. The implications of these advances for the future of sleep research are summarized.

Animals↗

Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster.

The central clock is generally thought to provide timing information for rest/activity but not to otherwise participate in regulation of these states. To test the hypothesis that genes that are components of the molecular clock also regulate rest, the authors quantified the duration and intensity of consolidated rest and activity for the four viable Drosophila mutations of the central clock that lead to arrhythmic locomotor behavior and for the pdf mutant that lacks pigment-dispersing factor, an output neuropeptide. Only the cycle (cyc01) and Clock (Clk(Jrk)) mutants had abnormalities that mapped to the mutant locus, namely, decreased consolidated rest and grossly extended periods of activity. All mutants with the exception of the cyc01 fly exhibited a qualitatively normal compensatory rebound after rest deprivation. This abnormal response in cyc01 was sexually dimorphic, being reduced or absent in males and exaggerated in females. Finally, the cyc01 mutation shortened the life span of male flies. These data indicate that cycle regulates rest and life span in male Drosophila.

ARNTL Transcription Factors↗