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 Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>