Light Therapy

Laser Light Zaps Away Cocaine Addiction

Posted on Sep 28, 2013

Laser Light Zaps Away Cocaine Addiction

By stimulating one part of the brain with laser light, researchers at the National Institutes of Health (NIH) and the Ernest Gallo Clinic and Research Center at UC San Francisco (UCSF) have shown that they can wipe away addictive behavior in rats – or conversely turn non-addicted rats into compulsive cocaine seekers.  “When we turn on a laser light in the prelimbic region of the prefrontal cortex, the compulsive cocaine seeking is gone,” said Antonello Bonci, MD, scientific director of the intramural research program at the NIH’s National Institute on Drug Abuse (NIDA), where the work was done. Bonci is also an adjunct professor of neurology at UCSF and an adjunct professor at Johns Hopkins University. Described this week in the journal Nature, the new study demonstrates the central role the prefrontal cortex plays in compulsive cocaine addiction. It also suggests a new therapy that could be tested immediately in humans, said Billy Chen of NIDA, the lead author of the study. Any new human therapy would not be based on using lasers, but would most likely rely on electromagnetic stimulation outside the scalp, in particular a technique called transcranial magnetic stimulation (TMS). Clinical trials are now being designed to test whether this approach works, Chen added. The High Cost of Cocaine Abuse Cocaine abuse is a major public health problem in the United States today, and it places a heavy toll on society in terms of lost job productivity, lost earnings, cocaine-related crime, incarcerations, investigations, and treatment and prevention programs. Antonello Bonci, MD The human toll is even greater, with an estimated 1.4 million Americans addicted to the drug. It is frequently the cause of emergency room visits – 482,188 in 2008 alone – and it is a top cause of heart attacks and strokes for people under 35. One of the hallmarks of cocaine addiction is compulsive drug taking – the loss of ability to refrain from taking the drug even if it’s destroying one’s life. What makes the new work so promising, said Bonci, is that Chen and his colleagues were working with an animal model that mimics this sort of compulsive cocaine addiction. The animals, like human addicts, are more likely to make bad decisions and take cocaine even when they are conditioned to expect self-harm associated with it. Electrophysiological studies involving these rats have shown that they have extremely low activity in the prefrontal cortex – a brain region fundamental for impulse control, decision making and behavioral flexibility. Similar studies that imaged the brains of humans have shown the same pattern of low activity in this region in people who are compulsively addicted to cocaine. Altering Brain Activity with a Laser To test whether altering the activity in this brain region could impact addiction, Chen and his colleagues employed a technique called optogenetics to shut the activity on and off using a laser. First they took light-sensitive proteins called rhodopsins and used genetic engineering to insert them into neurons in the rat’s prefrontal cortex. Activating this region with a laser tuned to the rhodopsins turned the nerve cells on and off. Turning on these cells wiped out the compulsive behavior, while switching them off turned the non-addicted ones into addicted, researchers found. What’s exciting, said Bonci, is that there is a way to induce a similar activation of the prelimbic cortex in people through a technique called transcranial magnetic stimulation (TMS), which applies an external electromagnetic field to the brain and has been used as a treatment for symptoms of depression. Bonci and his colleagues plan to begin clinical trials at NIH in which...

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Incredible light-controlled proteomics could revolutionize both medicine and research

Posted on Sep 24, 2013

Incredible light-controlled proteomics could revolutionize both medicine and research

Researchers have taken a particular protein-protein interaction involved in endocytosis, studied the sequences involved, and designed photo-switchable inhibitors to selectively turn a physiological process on and off. What’s truly amazing about this study is the process they used to get there. In studying endocytosis, the researchers have given us a path to control any number of protein-protein interactions.  If you know enough about the components involved, with enough work you could design versions of these small proteins, so-called “Traffic Light” peptides, to reversibly give that interaction a control switch. The most important discoveries in science are sometimes those of direct application — penicillin, the transistor — but more often than not they are the ones that simply facilitate more, or better research in the future. Nobel Prizes have gone to the creators of graphene, despite a near total lack of practical applications as of yet. An earlier Nobel went to researchers investigating a tiny, fluorescent jellyfish protein, seemingly useless at the time, and today that protein is foundational to thousands of papers in genetics. A similar sort of attention is beginning to fall on the field of optogenics, the control of single neurons, despite its continuing infancy as a practical technique. We understand that the real work comes in flinging open a door, even if it ends up being someone else who actually steps through it. The primary form of optogenics right now uses pulses of light to induce particular neurons to fire at the precise moment we desire. It’s an incredible breakthrough, and though it’s incalculably more elegant and precise than what came before it (caveman stuff like burning out whole neurons forever) it’s still a fairly blunt process. All it really does is grow neurons with a particular type of ion channel that changes shape under blue light — blue light goes on, channels open, neuron fires. That’s a huge step forward, but it’s one dimensional; there aren’t too many other processes that work so reliably based on a simple open-close dynamic. But what if even complex tasks, interactions between more than one protein, could be controlled in much the same way? This month, the German chemical journal of reference Angewandte Chemie will give its coveted Very Important standing to a paper detailing how to do just that.  The researchers have taken a particular protein-protein interaction involved in endocytosis, studied the sequences involved, and designed photo-switchable inhibitors to selectively turn this process on and off. This is an important pathway in the cell, one with implications for everything from diabetes to cancer, but it’s only the beginning. As discussed, what’s truly amazing about this study is the process they used to get there. In studying endocytosis, the researchers have given us a path to control any number of protein-protein interactions. If you know enough about the components involved, with enough work you could design versions of these small proteins, so-called “Traffic Light” peptides, to reversibly give that interaction a control switch. Pay no attention to the foreign walk signals. What you see here is an important breakthrough in our ability to control the behavior of cells. The applications here are almost literally endless. Perhaps, rather than relying on a geriatric’s unreliable memory for strict dosage self-monitoring, we could keep circulating blood levels high and let a computer simply turn on or off the liver’s ability to take it up.  We could replace five small doses per day, many of which are missed or taken at slightly the wrong time, with a single daily dose used over five computer-precise uptake events.  If we know of a particular cluster...

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