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| Is this peptide a key to happiness? Posted: 06 Mar 2013 09:00 PM PST What makes us happy? Family? Money? Love? How about a peptide? The neurochemical changes underlying human emotions and social behavior are largely unknown. Now though, for the first time in humans, scientists at UCLA have measured the release of a specific peptide, a neurotransmitter called hypocretin, that greatly increased when subjects were happy but decreased when they were sad.
The finding suggests that boosting hypocretin could elevate both mood and alertness in humans, thus laying the foundation for possible future treatments of psychiatric disorders like depression by targeting measureable abnormalities in brain chemistry. In addition, the study measured for the first time the release of another peptide, this one called melanin concentrating hormone, or MCH. Researchers found that its release was minimal in waking but greatly increased during sleep, suggesting a key role for this peptide in making humans sleepy. The study is published in the March 5 online edition of the journal Nature Communications. “The current findings explain the sleepiness of narcolepsy, as well as the depression that frequently accompanies this disorder,” said senior author Jerome Siegel, a professor of psychiatry and director of the Center for Sleep Research at UCLA’s Semel Institute for Neuroscience and Human Behavior. “The findings also suggest that hypocretin deficiency may underlie depression from other causes.” In 2000, Siegel’s team published findings showing that people suffering from narcolepsy, a neurological disorder characterized by uncontrollable periods of deep sleep, had 95 percent fewer hypocretin nerve cells in their brains than those without the illness. The study was the first to show a possible biological cause of the disorder. Since depression is strongly associated with narcolepsy, Siegel’s lab began to explore hypocretin and its possible link to depression. Depression is the leading cause of psychiatric disability in the U.S, Siegel noted. More than 6 percent of the population is affected each year, with lifetime prevalence exceeding 15 percent. Yet the use of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), has not been based on evidence of a deficiency, or excess, of any neurotransmitter. Several recent studies have questioned whether SSRIs, as well as other depression-fighting drugs, are any more effective than placebos. In the current study, the researchers obtained their data on both hypocretin and MCH directly from the brains of eight patients who were being treated at Ronald Reagan UCLA Medical Center for intractable epilepsy. The patients had been implanted with intracranial depth electrodes by Dr. Itzhak Fried, a UCLA professor of neurosurgery and psychiatry and a co-author of the study, to identify seizure foci for potential surgical treatment. The location of electrodes was based solely on clinical criteria. The researchers, with the patients’ consent, used these same electrodes to “piggyback” their research. A membrane similar to that used for kidney dialysis and a very sensitive radioimmunoassay procedure were used to measure the release of hypocretin and MCH. The patients were recorded while they watched television; engaged in social interactions such as talking to physicians, nursing staff or family; ate; underwent various clinical manipulations; and experienced sleep?wake transitions. Notes of activities were made throughout the study every 15 minutes in synchrony with a 15-minute microdialysis sample collection by a researcher in the patients’ rooms. The subjects rated their moods and attitudes on a questionnaire, which was administered every hour during waking. The researchers found that hypocretin levels were not linked to arousal in general but were maximized during positive emotions, anger, social interactions and awakening. In contrast, MCH levels were maximal during sleep onset and minimal during social interactions. “These results suggest a previously unappreciated emotional specificity in the activation of arousal and sleep in humans,” Siegel said. “The findings suggest that abnormalities in the pattern of activation of these systems may contribute to a number of psychiatric disorders.” Siegel noted that hypocretin antagonists are now being developed by several drug companies for use as sleeping pills. The current work suggests that these drugs will alter mood as well sleep tendency. The Siegel lab has also previously reported that hypocretin is required for the “pursuit of pleasure” in rodents but plays no role in avoidance behavior. “These results, in conjunction with the current findings, suggest that hypocretin administration will elevate both mood and alertness in humans,” Siegel said. ### Other authors on the study were Ashley M. Blouin, Charles L. Wilson, Richard J. Staba, Eric J. Behnke, Hoa A. Lam, Nigel T. Maidment, Karl Æ. Karlsson and Jennifer L. Lapierre. Funding was provided by National Institutes of Health grants MH064109, NS14610, NS33310 and NS02808 and by the Medical Research Service of the Department of Veterans Affairs. The UCLA Department of Psychiatry and Biobehavioral Sciences is the home within the David Geffen School of Medicine at UCLA for faculty who are experts in the origins and treatment of disorders of complex human behavior. The department is part of the Semel Institute for Neuroscience and Human Behavior at UCLA, a world-leading interdisciplinary research and education institute devoted to the understanding of complex human behavior and the causes and consequences of neuropsychiatric disorders. For more news, visit the UCLA Newsroom and follow us on Twitter. Contact: Mark Wheeler |
| Killing cancer cells with acid reflux Posted: 05 Mar 2013 09:00 PM PST A University of Central Florida chemist has come up with a unique way to kill certain cancer cells ? give them acid reflux. Chemistry professor Kevin Belfield used a special salt to make cancer cells more acidic ? similar to the way greasy foods cause acid reflux in some people. He used a light-activated, acid-generating molecule to make the cells more acidic when exposed to specific wavelengths of light, which in turn kills the bad cells. The surrounding healthy cells stay intact.
The technique is a simple way around a problem that has frustrated researchers for years. For photodynamic therapy (the special laser-light treatment) to work, cancer cells loaded with photosensitizers need oxygen to trigger the fatal reaction. But by their very nature, most cancer cells lack oxygen. Nonetheless, scientists were intent on making the photodynamic system work because it offers a way to target cancer cells deep within human tissue without causing a lot of collateral damage. Instead of focusing on oxygen, Belfield flipped the problem around and found another way to poison the bad cells, while protecting the healthy ones. “It’s the first time we’ve found a way around the oxygen problem,” Belfield said. “This work is truly ground breaking. It should eventually provide a therapeutic means to treat certain types of cancers with minimal side effects. It should also be a very useful tool for cell biologists and biomedical researchers. It could even find a place in treating other diseases such as neurodegenerative diseases.” His work was recently published in the Journal of the American Chemical Society. (http://pubs.acs.org/doi/full/10.1021/ja3122312) Belfield and his team at UCF used human colorectal carcinoma cells for the study, which was funded by the National Science Foundation and the National Institutes for Health. More research is needed to determine that there are no serious side affects in humans and whether the technique will work on a variety of cancers, but Belfield is optimistic. “Predicting commercialization is difficult at best,” he said. “But we are well situated to forge ahead”. So how did Belfield come up with such an “outside the box” approach? His other non-medical related research was the inspiration. Belfield has developed a three-dimensional, optical data-storage system, which involves the use of acid generators. About six years ago he wondered if his approach could have applications in medical therapy. “It took about five years to get someone in my research group interested to take on the unorthodox project,” Belfield said. “But it seems to have paid off.” Other contributors to the research are Xiling Yue, Ciceron O. Yanez and Sheng Yao, researchers and students at UCF students focusing on chemistry or photonics. Belfield is one of the pioneers in two-photon absorbing materials, two-photon photochemistry, and two-photon photophysics. His research spans a number of disciplines including organic, polymer, and physical chemistry, as well as optics, optical microscopy, and bioimaging. His research has potential applications in everything from the way people store data on DVDs to fighting cancer. ### 50 Years of Achievement: The University of Central Florida, the nation’s second-largest university with nearly 60,000 students, is celebrating its 50th anniversary in 2013. UCF has grown in size, quality, diversity and reputation, and today the university offers more than 200 degree programs at its main campus in Orlando and more than a dozen other locations. Known as America’s leading partnership university, UCF is an economic engine attracting and supporting industries vital to the region’s success now and into the future. For more information, visit http://today.ucf.edu. Contact: Zenaida Gonzalez Kotala |
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