*Autoimmunity plays major role in triggering narcolepsy process*

The exact cause of the condition, which affects about one in 3,000 people, has long eluded scientists.

By
April 18, 2015 21:42
DR. AVITAL Porter and patient

DR. AVITAL Porter and patient. (photo credit: BINYAMIN ADAM)

People suffering from the as yet untreatable condition of narcolepsy suffer from bouts of sleepiness that make it difficult for them to function normally.

The exact cause of the condition, which affects about one in 3,000 people, has long eluded scientists.

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Now a new study published in the journal Pharmacological Research by leading autoimmune disease expert Prof. Yehuda Shoenfeld of Tel Aviv University’s Sackler Faculty of Medicine maintains that narcolepsy bears the trademarks of a classic autoimmune disorder and should be treated accordingly. The research was led by Shoenfeld, who heads the center for autoimmune diseases at Sheba Medical Center, and was conducted by doctoral student María-Teresa Arango.

They found that a particular autoimmune process is the trigger for the loss of orexin neurons, which maintain the delicate equilibrium between sleep and wakefulness in the brain.

“Narcolepsy is interesting, because although it has been considered to be strictly genetic, it is induced by environmental factors, such as a burst of laughter or stress,” said Shoenfeld. “Narcolepsy is devastating to those suffering from it and debilitating, in particular, to children.”

Narcolepsy first strikes people aged 10 to 25, plaguing them for life. Narcoleptics may experience any or all of the following symptoms – falling asleep without warning anywhere, anytime, making it difficult to concentrate and function; excessive daytime sleepiness; sudden loss of muscle tone; slurred speech or weakness of most muscles for a few seconds or minutes; a temporary inability to move or speak while falling asleep or upon waking; and hallucinations.

Shoenfeld first became interested in the subject after an avalanche of narcolepsy diagnoses swept Finland in 2009 following the administering of the H1N1 flu vaccine. After the use of this vaccine, 16 times the average incidence of narcolepsy was reported, said Shoenfeld.

He discovered that a group of researchers from the sleep control project at the Tokyo Metropolitan Institute of Psychiatry had published a study on an autoantibody presence attacking tribbles (small granules in the brain containing regulatory orexin neurons, which maintain the balance between sleep and wakefulness).

“In patients and animals that develop narcolepsy, we have seen an evident depletion of orexin in the brain, and therefore a lack of balance, and later attacks of narcolepsy,” noted Shoenfeld. “Why is the orexin disappearing? We think the culprit is an autoimmune reaction – the binding of autoantibodies to the tribble granules to destroy them.”

For the new study, Shoenfeld and his team collaborated with the Japanese research group, led by Dr. Makoto Honda, to isolate the specific antibodies, which were then injected directly into laboratory mice. Arango monitored their behavior for several months, tracking their sleep patterns.

“What we saw was an increased number of sleep attacks and irregular patterns of sleep in mice,” said Shoenfeld.

“Mice fall asleep like dogs, circling around before going to sleep. Suddenly, in this experiment, the mice just dropped off to sleep and then, just two minutes later, woke up as though nothing had happened. Our hope is to change the perception and diagnosis of narcolepsy, to define it as the 81st known autoimmune disease.”

“A better understanding of the mechanism causing this disease, which debilitates and humiliates so many people, will lead to better treatment and, maybe one day, a cure,” he concluded.

BRAIN STRUCTURE AND TRUST

The structure of the brain varies according to how trusting people are of others, according to a new study at the University of Georgia. The research may have implications for future treatments of psychological conditions such as autism, said the study’s lead author, psychology Prof. Brian Haas.

Each autism diagnosis is on a spectrum and symptoms vary, but some diagnosed with the condition exhibit problems trusting other people.

“There are conditions such as autism that are characterized by deficits in being able to process the world socially, one of which is the ability to trust people,” Haas said. “Here we have converging evidence that these brain regions are important for trust and that if we can understand how these differences relate to specific social processes, we may be able to develop more targeted treatment techniques for people who have deficits in social cognition.”

Haas’s team examined 82 study participants, who filled out a self-reported questionnaire about their tendency to trust others. They also were shown pictures of faces with neutral facial expressions and asked to evaluate how trustworthy they found each person in the picture.

Researchers then took MRI scans of the participants’ brains to determine how brain structure is associated with the tendency to be more trusting. What researchers found, said Haas, were differences in two areas of the brain.

“The most important finding was that the grey matter volume was greater in the ventral medial prefrontal cortex, which is the brain region that serves to evaluate social rewards, in people that tended to be more trusting of others,” he said.

“Another finding that we observed was for a brain region called the amygdala. The volume of this area of the brain, which codes for emotional saliency, was greater in those that were both most trusting and least trusting of others. If something is emotionally important to us, the amygdala helps us code and remember it.”

Future studies may focus on how, and if, trust can be improved and whether the brain is malleable according to the type of communication someone has with another, he said.

TOBACCO SMOKE MAKES SUPERBUGS STRONGER

Methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant superbug, can cause life-threatening skin, bloodstream and surgical-site infections, as well as pneumonia. Researchers at the University of California at San Diego’s School of Medicine now report that cigarette smoke may make matters worse. The study, published March 30 in Infection and Immunity, shows that MRSA bacteria exposed to cigarette smoke become even more resistant to the immune system.

“We already know that smoking cigarettes harms human respiratory and immune cells, and now we’ve shown that, on the flipside, smoke can also stress out invasive bacteria and make them more aggressive,” said senior author Dr. Laura Crotty Alexander, a pulmonologist with many patients who smoke. She also sees many MRSA infections, and that got her wondering if one might influence the other.

To test the hypothesis, Crotty Alexander and her team infected macrophages – immune cells that engulf pathogens – with MRSA. Some of the bacteria were grown normally and some were grown with cigarette smoke extract. They found that while the macrophages were equally able to take up the two bacterial populations, they had a harder time killing the MRSA that had been exposed to cigarette smoke extract.

To better understand why, the team tested the bacteria’s susceptibility to individual mechanisms macrophages typically employ to kill bacteria. Once inside macrophages, smoke-exposed MRSA were more resistant to killing by reactive oxygen species, the chemical burst that macrophages use to destroy their microbial meals. The team also discovered that smoke-exposed MRSA were more resistant to antimicrobial peptides, small protein pieces the immune system uses to poke holes in bacterial cells and trigger inflammation. The effect was dose-dependent, meaning that the more smoke extract they used, the more resistant the MRSA became.

MRSA treated with cigarette smoke extract were also better at sticking to and invading human cells grown in the lab. In a mouse model, MRSA exposed to cigarette smoke survived better and caused pneumonia with a higher mortality rate.

The data suggest that cigarette smoke strengthens MRSA bacteria by altering their cell walls in such a way that they are better able to repel antimicrobial peptides and other charged particles.

“Cigarette smokers are known to be more susceptible to infectious diseases. Now we have evidence that cigarette smoke-induced resistance in MRSA may be an additional contributing factor,” Crotty Alexander said.


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