By MedPage Today Staff
A major symptom of depression is anhedonia — the inability to feel pleasure – and experiments in mice may have uncovered a possible new target to relieve the problem, according to a study in Nature.
In mice, melanocortin, an appetite-related hormone, turns off the brain’s capability to experience pleasure under chronic stressful conditions, which are often involved in depression, Robert Malenka, of Stanford University in Palo Alto, Calif., and colleagues found.
Melanocortin worked on the nucleus accumbens, a part of the brain that contains the reward circuit. When the mice were confined in small conical tubes for three to four hours a day, the capability of the animals to feel pleasure was reduced, as indicated by a weaker preference for sugar water over plain water. The results were similar when cocaine was used.
Blocking the stress-induced increases in melanocortin receptors in the mice prevented the development of anhedonia, suggesting that the hormone could be a potential target for depression.
There are already melanocortin inhibitors available that could be used for clinical trials, the researchers noted.
Sunburn arises from an inflammatory immune response to RNA damage, researchers found.
Using human skin cells and a mouse model, the skin-reddening ultraviolet (UV) B rays were shown to fracture and tangle noncoding micro-RNA. Surrounding healthy cells then reacted to begin the inflammatory process that would remove their damaged neighbor, the group reported in Nature Medicine.
While this inflammatory process generally is supposed to rid the body of cells that could lead to cancer, finding a way around it could help prevent problems in some cases.
“For example, diseases like psoriasis are treated by UV light, but a huge side effect is that this treatment increases the risk of skin cancer,” lead author Richard L. Gallo, MD, PhD, of the University of California San Diego and the VA San Diego Healthcare System, noted in a press release.
“Our discovery suggests a way to get the beneficial effects of UV therapy without actually exposing our patients to the harmful UV light,” he explained. “Also, some people have excess sensitivity to UV light, patients with lupus, for example. We are exploring if we can help them by blocking the pathway we discovered.”
Protein Might Clean Up Huntington’s Damage
A protein that plays a role in regulating mitochondria might offer a therapeutic approach to Huntington’s disease, according to researchers led by Albert La Spada, MD, PhD, of the University of California San Diego.
Huntington’s — caused by an inherited mutation in the huntingtin gene that leads to the accumulation of misfolded proteins in neurons – is characterized by deterioration of involuntary movement control, cognitive decline, and psychological problems.
The protein PGC-1alpha helps regulate mitochondria, the energy source of all cells, including neurons, but when it’s missing in mice, they develop symptoms similar to those of Huntington’s – neurological abnormalities and neurodegeneration.
In a mouse model of Huntington’s, over-expressing the protein prevented the accumulation of misfolded proteins that characterizes the disease, the researchers reported in Science Translational Medicine. Moreover, the animals continued to behave normally, suggesting that the finding opens a door to potential therapy for Huntington’s, the researchers argued.
Stenting Disrupts Coronary Vessel Function
Drug-eluting stents appear to cause early and sustained microvascular damage following percutaneous coronary intervention (PCI), but other stenting devices such as bare-metal stents, drug-eluting balloons, or plain balloons are not immune from temporary damage, according to an animal study reported in the Journal of the American College of Cardiology.
In the study, pigs underwent PCI with various stenting devices. Artery vasodilation and vasoconstriction were significantly decreased in all treated vessels, compared with untreated controls at 5 hours post PCI. At 1-month follow-up, however, this impairment remained significant only for arteries treated by drug-eluting stents, according to Christian A. Plass, MD, from the Medical University of Vienna in Austria, and colleagues.
The use of drug-eluting stents also dampened new endothelial growth compared with the other PCI devices.
Researchers concluded that there was a time-dependent impairment of vasodilation and vasoconstriction post-PCI “with slow recovery, which might influence the long-term outcome of PCI, regarding restenosis, vessel remodeling, and thrombosis.”
Public, Private Organizations Gang Up on Food Pathogens
A joint venture between the FDA, University of California Davis, Agilent Technologies, and the CDC will create a free, public, 100,000 genome sequence-strong database of food pathogens.
The database will grant researchers to “help speed the identification of bacteria responsible for foodborne outbreaks,” as well as speed up response time, the FDA stated in a statement. Having thousands of genome sequences publicly available can “provide a road map” to the creation of new diagnostic tests, which currently take roughly a week to identify pathogens in a sample, the bureau added.
The database also would potentially help identify where an outbreak may have originated by indicating where a specific strain was last seen.
The FDA, UC Davis, and CDC are each providing strain samples, while Agilent is supplying funding and instruments for the project. The database will be available through the NIH’s National Center for Biotechnology Information.
Small noncoding molecules of RNA known as microRNAs that serve a regulatory function in gene expression have been shown to help encourage metastatic spread in cancer cells, targeting messenger RNA with cell-to-cell communication. But researchers from Ohio State University now have discovered that these small RNA molecules secreted by tumor cells have an additional mechanism of action, in that they can act as ligands for toll-like receptors in both murine and human immune cells.
Binding to these receptors results in an inflammatory cascade, upregulating the tumor microenvironment, and opening the door to metastatic spread, explained Muller Fabbri, PhD, and colleagues.
They demonstrated the effects of this process by injecting mice with primary tumors and no gene for toll-like receptor 7 with lung cancer cells. The result was a significantly greater number of tumor metastases than was seen in mice carrying the toll-like receptor gene (14 versus 4).
“These data confirm the importance of TLR7 activation in the development of lung cancer multiplicities,” the researchers wrote in the Proceedings of the National Academy of Sciences. The elucidation of this means of molecular spread by tumor cells may represent a potential new target for antitumor treatments, through manipulation of specific microenvironments, they concluded.
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Submited at Saturday, July 14th, 2012 at 12:15 am on Uncategorized by jessica
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