Saturday, April 9, 2016

Highlights and new discoveries in Neuroscience (March 2016)


n the third issue of this monthly digest series you can find out where the root of all evil lies in the brain, how researchers plan to prevent Alzheimer's disease, why you should eat blueberries, and much more.

The key to both Alzheimer's and Parkinson's?

This March saw two breakthroughs in the fight against Alzheimer's and Parkinson's disease.

Using latest-generation molecular simulations, researchers from the IMIM (Hospital del Mar Medical Research Institute), Pompeu Fabra University, and University of Tampere (Finland) demonstrated that a decrease in polyunsaturated lipids in neuronal membranes, as seen in Parkinson's and Alzheimer's sufferers, directly affects the binding rate of dopamine and adenosine receptors. These are part of the family of receptors connected to the G protein (GPCR), located in the cell membrane and responsible for transmitting signals to within the cell. Until now, various studies have demonstrated that lipid profiles in the brains of people with diseases like Alzheimer's and Parkinson's are very different from those of healthy people. These studies showed that the levels of a polyunsaturated fatty acid in neuronal membranes are considerably lower in the brains of sufferers. The researchers believe that this difference in the lipid composition of membranes could alter the way in which certain proteins interact with each other, as in the case of the GPCR receivers. These results will enable, in the future, new therapeutic pathways to be initiated for regulating the binding of these receivers, either through the lipid composition of the membrane or by designing new lipids that have a modulating effect on this binding rate.

Meanwhile at EPFL in Lausanne, Switzerland, researchers from the Brain Mind Institute developed a bioactive capsule that can clean out the "toxic junk" when implanted in mouse brains. Alzheimer's disease can actually take shape even decades before the first signs of dementia strike, by building amyloid plaques—toxic protein clumps that clog the brain's waste disposal system and wreak havoc on the delicate molecular machinery that underlies our memories, our history, and our personality. Currently, these plaques are fought by flooding the brain (passive immunization) with antibodies that prevent amyloid proteins from clumping. The problem with this is that most antibody injections need to be given at extremely high doses to have even a moderate effect. In addition, there are side effects that can tamper with the brain's normal functioning.

The solution, now made possible by researchers at EPFL, is to deliver the therapeutics in a small and targeted dosage. A bioactive capsule—about an inch long and packed with genetically engineered cells that steadily pump out anti-amyloid antibodies—is implanted under the skin of susceptible patients long before the first signs of cognitive decline strike. In their studies, when they implanted the capsule into young mice, the encapsulated cells steadily synthesized anti-amyloid antibodies for 10 months and significantly reduced pathological signs of protein clumps in the brain later in life. When the scientists looked into the mice's brains, they found that the antibodies had tagged onto the amyloid proteins, sending out a warning call to the local immune system. Further, they saw microglia—specialized immune cells that patrol the brain and gobble up waste—had burst into activity, engulfing toxic amyloid clumps much more efficiently than microglia from control mice. As a result, toxic plaque buildup was reduced by roughly 95% (compared to control mice) ten months after implantation.

Although just the first step, this study solves one of the thorniest issues plagueing the disease—prevention. The microcapsule offers a way to begin treatment early, instead of passively reacting to the toxic protein buildup cascade.

Source: Science Daily, Huffington Post.

The root of all evil

Dr. Dayu Lin and colleagues from the NYU Langone Medical Center have uncovered a distinct part of the brain that fires up right before premeditated nefarious acts are carried out.

In their experiments, the researchers trained male mice to attack weaker male mice and subsequently monitored their behavior. They first had other male mice intrude on their territory to establish a baseline for their aggression-seeking behavior. They then removed the intruder from the box, and taught the mice that there are two panels in the walls of the box that they can nose-poke: If mice poked the designated 'social' port during training, they received free access to a submissive, highly defeated male for a short interaction. Poking the second 'null' port triggered no interaction event. This setup made it possible to separate the resident-intruder procedure from the social interaction, so that brain regions lighting up during social interactions wouldn't interfere with their result.

The mice were fitted probes that were used to measure brain activity right before, during, and after they planned an attack. What the researchers found was that, just before the aggressive mice began to hole poke, even when they could not yet smell or see the target, a particular brain region known as the ventrolateral part of the ventromedial hypothalamus (VMHvl) lid up. The hypothalamus is a brain structure that is found in all vertebrates, and its activity is linked to the regulation of hormone secretion, body temperature, hunger, and sleep. Neural activity in the VMHvl also increased by as much as tenfold during the initial seconds after the weaker target mice appeared. Interestingly, when they genetically inactivated the VMHvl, the aggressive mice actually stopped attacking weaker mice.

The researchers say it is possible that the region is linked to reward centers of the brain which make an attack seem more desirable and may promote a flow of endorphins. Previous studies have shown that before a fight, dopamine levels rise in the brain and remain elevated after an attack has ended, which leads to a decrease in pain and an increase in adrenaline.

First author Dr. Falkner points out that, even though several brain areas have been implicated in the generation of an attack in response to social threats, little is known about the neural mechanisms that promote self-initiated or "voluntary" aggression-seeking behavior when no threat is present. Future research will have to shed light on that one.

Source: Nature Neuroscience, Telegraph.

Newborn neurons observed in a live brain for first time

For a long time, it was thought that we are born with all the brain cells we'll ever have. Now we know that certain regions of the brain continue to make new neurons throughout life. Slices of brain tissue show that most of these are created in the hippocampus—a seahorse-shaped structure known to be crucial for learning and memory. Yet, until now, we had never seen these neurons in action in a live animal.

Attila Losonczy at Columbia University Medical Center in New York and his colleagues combined several techniques to achieve the feat. They first implanted a device that included a miniature microscope into the brains of live mice. They also modified the mice so that newly made neurons would glow. The team were able to watch the activity of the cells while performing experiments on the mice to explore their function. In one, the mice ran on a treadmill while the team tweaked the surrounding sights, smells and sounds. For instance, the mice might hear low tones, smell a banana scent and see a blue light. Other times they would smell a lemon scent and see a blinking light. The team paired a small electric shock with some of the cues, so that the mice learned to associate these cues with an unpleasant experience.

The researchers then deactivated the new neurons using optogenetics, which switches off specific cells using light. Once they had done this, the mice were unable to tell the difference between the scary and safe cues, and ended up being fearful of them all. "They couldn't tell apart these similar, but different, contexts," says Losonczy.

The finding suggests that newborn cells in adult animals may play a role in telling apart and separating memories.

Source: New Scientist.


People with anxiety fundamentally perceive the world differently, according to a study reported in Current Biology. The new study shows that people diagnosed with anxiety are less able to distinguish between a neutral, "safe" stimulus (in this case, the sound of a tone) and one that was earlier associated with the threat of money loss or gain. In other words, when it comes to emotional experiences, they show a behavioral phenomenon known as over-generalization, the researchers say. The findings might help to explain why some people are more prone to anxiety than others, although the underlying brain plasticity that leads to anxiety isn't in itself "bad", says Rony Paz of Weizmann Institute of Science in Israel. (Science Daily; Image credit Katie Crawford)

Researchers at the University of Western Australia discovered that nutrition in early childhood may have a long-term association with fundamental cognitive processing speed, which is likely to be related to enhanced brain development in the first year of life. They found that boys who had been breastfed for 4 months or longer showed better cognitive performance with regard to psychomotor speed. A healthier diet during infancy may in fact exert long-lasting cognitive benefits. (Frontiers in Nutrition)

Eating blueberries could help improve memory and cognitive function, a new study found. Researchers recruited 47 older adults with mild cognitive impairment. Some of them had the equivalent of a cup of blueberries in powder form each day for 16 weeks, whereas others had a placebo powder. The blueberry group demonstrated improved memory and improved access to words and concepts, adding further support to the notion that blueberries can have a real benefit in improving memory and cognitive function in some older adults. (Spring)

Next month

Things to look out for in April:

Anything I missed? Sound away in the comment section! Have something of interest or want your discovery to be considered for next month's issue? Let me know via mbeyeler (at) uci (dot) edu.

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