DEPRESSION UNMASKED
Researchers have found a single brain circuit that can help explain depression and lead to new treatment
Mice with herpes get immune-system boost
WASHINGTON
Laboratory mice infected with herpes seem better able to resist bacteria that cause the plague and food poisoning, suggesting an unexpected immune-system boost from contracting the virus.
Nature reported that scientists at Washington University School of Medicine in Saint Louis, Missouri, theorize that chronic herpes infection may have fundamentally altered the mice's immune systems at a fundamental level, or might have established a "symbiotic relationship" within their bodies. Either way, it means that there could actually be a positive health benefit in contracting the disease.
"Our results suggest that we should look at whether humans receive similar advantages from these and other chronic infections that do not cause active disease," said senior author Herbert Virgin. "If so, that has public-health implications because we would want to very carefully weigh the risks and benefits of eliminating a virus that our bodies have established a symbiotic relationship with," he said, urging further research to better understand the exact mechanisms that underlie the process.
Scientists find "Holy Grail" of depression
WASHINGTON
Scientists and doctors long baffled by the multiple causes and brain processes for depression may now have a single "Holy Grail" brain pathway to focus on for treatment. Studying the brains of rats, researchers at the Stanford University School of Medicine have discovered a single brain circuit that appears to funnel all the mechanisms and treatments of depression.
Depression-related behavior is manifested in changes in electrical signals moving through the circuit, according to the study released online by Science.
Karl Deisseroth, a professor of bioengineering and of psychiatry and behavioral sciences, said the circuit can help explain why there can be many causes of and treatments for depression. "It also helps us understand conceptually how something that seems as hard to get traction on as depression can have a really quantitative, concrete basis," he said.
Deisseroth led a research team to see if they could demonstrate how malfunctions in brain circuitry could be at the root of depression. They studied the electrical activity of still-active slices of the hippocampus of rats treated with fluorescent dye, using high-speed, high-resolution cameras to record activity in brain neurons in real time.
Deisseroth said rat brains show similar depression symptoms to human ones and react to antidepressants in the same way. The testing showed that an alteration in electrical activity flow through the brain could be readjusted with the use of human drugs against depression-suggesting the existence of a specific circuit for the condition.
Deisseroth said the discovery of the single circuit for depression could help doctors come up with better methods to diagnose and quantify the problem in humans. "The Holy Grail of psychiatry is to try to find final common pathways that can make sense of how genes and life experiences end up with the same result," he said. "And the same goes for medications. There are many treatments that act in fundamentally different ways-how do we make sense of all that complexity?"
Testosterone helps battle multiple sclerosis
WASHINGTON
Testosterone, the mighty hormone that elevates physical energy and sex drive, can also help fight the effects in men of multiple sclerosis (MS), which weakens the body's immune and nervous systems.
Nancy Sicotte of the University of California-Los Angeles and a team of researchers found in a small pilot study on 10 men with MS that regular application of a gel containing testosterone helped their cognitive ability and slowed down brain deterioration characteristic of MS.
The 10 subjects, each with relapsing-remitting MS-in which the disease generates periodic neurological symptoms like numbness and difficulty moving around, and then falls into periods of remission-were given daily applications of the gel, containing 100 milligrams of testosterone, over 12 months.
Before the treatment the subjects showed on average an annual decrease in brain size due to MS of 0.81 percent. But after receiving the testosterone, brain atrophy slowed to 0.25 percent a year. Also, the participants enjoyed on average a 1.7-kilogram increase in muscle mass during the treatment, and reported no adverse effects.
"One year of treatment with testosterone gel was associated with improvement in cognitive performance and a slowing of brain atrophy," the authors of wrote. They also said that the successful use of testosterone to fight brain atrophy in men with MS suggests the same treatment might work with other noninflammatory neurodege-nerative diseases like amyotrophic lateral sclerosis or Lou Gehrig's disease.
The study was published in the May issue of Archives of Neurology.
Scientists eye an enzyme to fight autism
CHICAGO
Researchers have reversed the symptoms of mental retardation and autism in mice by inhibiting an enzyme that affects the connections between brain cells. In a series of experiments, researchers at the Massachusetts Institute of Technology showed that they could undo the brain damage seen in Fragile X syndrome (FXS) by inhibiting a key brain chemical called p21-activated kinase (PAK).
In humans, FXS is the leading cause of mental retardation and the most common genetic cause of autism. The study raises the intriguing possibility that the brain damage seen in children with autism can be rolled back, and identifies a specific target for potential drugs.
"It opens up a new avenue for drug research to treat this condition," said lead author Susumu Tonegawa, a neuroscientist at MIT in Cambridge, Massachusetts.
MIT researchers began by creating a batch of mice that had been genetically modified to have FXS, a condition in which the neurons of the brain are structurally abnormal and functionally impaired. These transgenic mice had many of the behavioral problems seen in kids with the condition: hyperactivity, attention deficits, repetitive behaviors, and poor social skills.
The investigators then crossbred these mice with another batch of mice that had been genetically modified to inhibit the activity of the PAK enzyme, which is instrumental in shaping the formation of neuronal connections in the brain.
The researchers knew that when PAK was inactivated, the mice developed neurons that had short, fat dendritic spines, with a higher-than-usual capacity for relaying the electrical impulses that pass between brain cells. In other words, the shape and function of the dendritic spines in the PAK mice was just the reverse of those seen in the brain cells of the mice with FXS. The researchers gambled that the two abnormalities would cancel each other out, and that's exactly what the experiment showed.
The crossbred mice had been genetically engineered so that the inactivation of the PAK enzyme began two weeks into the mouse's life cycle, which in human terms would be several years after birth. Tests and autopsies showed that the PAK-blocking action restored electrical communication between neurons in the brains of the double mutant mice, correcting their behavioral abnormalities in the process.
"This is very exciting because it suggests that PAK inhibitors could be used for therapeutic purposes to reverse already established mental impairments in fragile X children," said Eric Klann, a professor at New York University's Center for Neural Science.
The study, conducted by Tonegawa and a postdoctoral student at MIT's Picower Institute for Learning and Memory, appears in the Proceedings of the National Academy of Sciences.
TB enzyme points way to new drugs
CHICAGO
Swiss scientists said they have further evidence to suggest that an enzyme secreted by the microbe that causes tuberculosis would make a promising target for new drugs to combat the deadly disease.
The Swiss team first identified the enzyme, protein kinase G (PknG), as a promising drug target back in 2004. At the time, they said that the protein is the secret weapon that enables Mycobacterium tuberculosis to avoid being hunted down and destroyed by the body's immune-system sentinels as most other pathogens are. The protein apparently interferes with the functioning of macrophages that typically engulf and digest pathogens. Instead of absorbing and destroying the TB bacteria, the macrophages become host cells where the germ hides out.
In the same paper, the investigators said they had also identified a compound that could block the suspect protein, but they were concerned that by inhibiting this one protein, they would interfere with the action of other similar proteins secreted by the host cell.
"We wanted to be sure that inhibitors of mycobacterial PknG would not interefere with important host cellular functions," said lead author Prof. Jean Pieters of the University of Basel in Switzerland.
So Pieters and colleagues decided to examine the chemical structure of the PknG molecule and the compound that inhibits it in atomic resolution, using called X-ray crystallography. They found that the compound acted on a segment of the protein unique to PknG-not shared by any of the other 491 protein kinases that have been identified and sequenced.
Pieters said that new drugs targeting different pathways than those used by existing antibiotics should be able to sidestep various problems with existing TB drugs, specifically their inability to destroy the bacteria in their dormant form, which is one of the reasons that resistance has emerged.
The study appears in the Proceedings of the National Academy of Sciences.
Poor smell sense could signal Alzheimer's
WASHINGTON
People who have difficulty recognizing familiar smells could be experiencing an early sign of Alzheimer's disease, according to a study in the July issue of the Archives of General Psychiatry.
Scientists already know that the first lesions of the degenerative brain disease tend to show up in an area of the brain that is home to olfactory senses.
Doctors at the Rush University Medical Center in Chicago tested 589 people aged between 54 to 90, and asked them to identify 12 common odors such as lemon, chocolate, black pepper, banana, and soap. The subjects chose the best multiple choice answer for each. At the start of the study in 1997, none of the subjects had cognitive impairments. The participants were tested every year for five years, and over the course of the study, 30.1 percent developed mild cognitive impairment.
"Risk of developing mild cognitive impairment increased as odor identification decreased," said the authors. "Those who scored below average on the odor identification test were 50 percent more likely to develop the condition than those who scored above average. The findings suggest that olfactory dysfunction can be an early manifestation of Alzheimer's disease."
However, "the neurological bases of age-associated olfactory dysfunction are uncertain," and since "difficulty identifying odors is associated with other neurological diseases, including Parkinson's disease," further research was needed, the authors cautioned.
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