Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sundown Syndrome-Like Symptoms in Fruit Flies May Be Due to High Dopamine Levels Changes in Flies Parallel Human Disorder

15.05.2012
Perelman School of Medicine at the University of Pennsylvania researchers have discovered a mechanism involving the neurotransmitter dopamine that switches fruit fly behavior from being active during the day (diurnal) to nocturnal.
This change parallels a human disorder in which increased agitation occurs in the evening hours near sunset and may also be due to higher than normal dopamine levels in the brain. Sundown syndrome occurs in older people with dementia or cognitive impairment.

Many geriatricians have noted an association between sundown syndrome and changes in the internal biological clock among people with dementia, observing disruptions in their sleep-wake cycles. The internal clock, which guides rhythms over a 24-hour day, is connected to how active humans are at different times of the day.

The lab of Amita Sehgal, PhD, professor of Neuroscience and a Howard Hughes Medical Institute investigator, found that in fruit flies dopamine acts to arouse flies through a protein called cryptochrome that normally functions as a photoreceptor. Flies, like humans, are typically diurnal. The findings were released online this week in Genes & Development.

Using a strain of fly that has a mutated Clock (Clk) gene and exhibits nocturnal behavior, the team found that increased night-time activity of the Clk mutant flies is associated with elevated dopamine signaling. Specifically, Clk mutant flies have increased levels of an enzyme used to make dopamine called tyrosine hydroxylase in fly brains. The night-time behavior also requires the circadian photoreceptor, cryptochrome (CRY), in specific cells of the fly brain. These cells also express CLK, as do others that may be responsible for the elevated dopamine.

“Our results suggest that typically the dopamine pathway and CRY promote acute arousal. They allow an animal to respond to acute stimulation by sensory stimuli with a transient increase in activity,” says Sehgal. “However, chronic, increased signaling of the pathway leads to nocturnal activity, most likely because both CRY and dopamine activity are dampened by light.” A switched behavioral cycle is the result.

Based upon previous research and the present study, the Sehgal team proposed that CRY is required for two distinct acute responses -- acute arousal, which presumably awakens the animal, and resetting of the circadian clock in response to a pulse of light. This would fit with evolutionary needs as, even when they’re sleeping, animals need to be able to respond to sudden changes in the environment. It appears that both arousal, as well as circadian responses, to such sudden stimulation require the same molecule, says Sehgal.
The researchers also note parallels to these findings in mammals. Dopamine in mammals regulates melanopsin, a pigment in the retina important to synchronizing circadian cycles, much like CRY does in flies. Light-sensitive melanopsin is required to induce sleep in nocturnal rodents, who sleep during the day. In contrast, in humans, who are diurnal, mistimed elevated dopamine is linked to increased agitation and sleep disturbances in the early evening – the so-called sundown syndrome. “Although there are differences in CRY signaling between flies and humans, it is interesting to note that sundown syndrome is treated with medications that decrease the activity of dopamine,” says Sehgal.

She notes that the next step in this work would be to determine the molecular connection between dopamine and CRY and also to identify the mechanism by which CRY promotes arousal.

The research was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under grants 1R01NS048471 and 1R56NS048471. Co-authors in addition to Sehgal are Shailesh Kumar and Dechun Chen, both from Penn.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.

Karen Kreeger | Newswise Science News
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>