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Vol. LXVII, No. 11
May 22, 2015

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Souped-Up Remote Control Switches Behaviors On and Off in Mice

Neuroscientists have perfected a chemical-genetic remote control for brain circuitry and behavior. This evolving technology can now sequentially switch the same neurons—and the behaviors they mediate—on and off in mice, say NIH-funded researchers. Such bidirectional control is pivotal for decoding the brain workings of complex behaviors. The findings are the first to be published from the first wave of NIH grants awarded last fall under the BRAIN Initiative.

“With its new push-pull control, this tool sharpens the cutting edge of research aimed at improving our understanding of brain circuit disorders, such as schizophrenia and addictive behaviors,” said NIH director Dr. Francis Collins.

Dr. Bryan Roth of the University of North Carolina, Chapel Hill, and Dr. Michael Krashes of NIDDK and colleagues debuted the second generation of the tool, called DREADD (Designer Receptors Exclusively Activated by Designer Drugs) on Apr. 30 in the journal Neuron.

DREADD 2.0 improves on a widely adopted technology developed by Roth, an NIMH grantee, and colleagues over the past decade. It achieves remote control by introducing a synthetic brain chemical messenger system that integrates with the workings of naturally occurring systems.

Researchers genetically engineer mice to have brains containing what are dubbed “designer receptors” in specific circuits. These are synthetic proteins on the surface of neurons that can only be activated by a matching synthetic chemical that otherwise has no biological effect—like a lock that can only be opened by a unique key. When the “designer drug” binds to its receptor, depending on its programming, it either triggers or blocks neuronal activity, thus giving researchers experimental control over the animal’s brain circuits and behaviors.

No Evidence to Change Current Transfusion Practices for Adults Undergoing Complex Cardiac Surgery

An NIH-funded study found no statistical difference in the primary clinical measure—which assessed changes in function of six organs from before to 7 days after surgery—between complex cardiac surgery patients receiving transfusions of red blood cell units stored for short (up to 10 days) versus long (21 or more days) periods. These findings indicate there is no need to alter how hospitals currently transfuse blood in adults going through complex cardiac surgical procedures.

Results of the Red Cell Storage Duration Study (RECESS), supported by NHLBI, appeared Apr. 8 in the New England Journal of Medicine.

In the United States, red blood cell units can be stored up to 42 days after collection. Basic research has documented changes in red blood cell units the longer they are stored. Some studies, primarily observational, have found an association between the transfusion of blood stored for a longer duration and increased morbidity and mortality. However, the clinical significance of these findings is difficult to determine due to study-design limitations.

“RECESS contributes to a long-standing question about whether red blood cell storage duration impacts a patient’s clinical outcome after transfusion,” said Dr. Keith Hoots of NHLBI. “These findings are reassuring because they do not support the need to modify transfusion practices in adult patients undergoing complex cardiac surgery. In particular, there does not appear to be something gained by only transfusing red blood products stored for 10 days or less.”

Study Defines Brain, Behavioral Effects of Teen Binge Drinking

Photo of five adolescents lying on the grass

Adolescent binge drinking can disrupt gene regulation and brain development in ways that promote anxiety and excessive drinking behaviors that can persist into adulthood, according to a new study supported by NIAAA. A report of the study, conducted in animals by researchers at the University of Illinois at Chicago College of Medicine, appeared online in the journal Neurobiology of Disease.

“These findings are an important contribution to our understanding of the alcohol-induced brain changes that make alcohol problems in adulthood more likely among young people who abuse alcohol,” said NIAAA director Dr. George Koob.

Previous studies have shown that people who start drinking before the age of 15 are four times more likely to meet the criteria for alcohol dependence at some point in their lives; young people consume more than 90 percent of their alcohol by binge drinking.

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