Experimental Drug Improves Memory in Mice with Multiple Sclerosis

Johns Hopkins researchers report the successful use of a form of MRI to identify what appears to be a key biochemical marker for cognitive impairment in the brains of people with multiple sclerosis (MS). In follow-up experiments on mice with a rodent form of MS, researchers were able to use an experimental compound to manipulate that same marker and dramatically improve learning and memory.

Half of people with MS experience learning and memory problems, for which there is no approved treatment, along with movement abnormalities that characterize the debilitating autoimmune disorder.

"We have a potentially novel treatment for cognitive impairment in MS, a devastating condition on the rise that affects at least 400,000 people in the United States," says study leader Adam I. Kaplin, M.D., Ph.D., an assistant professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine.

Kaplin cautions that the treatment has so far been used only in mouse models of MS and is years away from clinical trials in people.

Nevertheless, he says, the research, described in the Proceedings of the National Academy of Sciences published online on Nov. 19, has the potential to speed development of new drugs to treat cognitive impairment not only in MS patients, but also in patients with Alzheimer’s disease and other neurological conditions.

Yeast Protein Breaks up Amyloid Fibrils and Disordered Protein Clumps In Different Ways

Several fatal brain disorders, including Parkinson’s disease, are connected by the misfolding of specific proteins into disordered clumps and stable, insoluble fibrils called amyloid. Amyloid fibrils are hard to break up due to their stable, ordered structure. For example, a-synuclein forms amyloid fibrils that accumulate in Lewy Bodies in Parkinson’s disease. By contrast, protein clumps that accumulate in response to environmental stress, such as heat shock, possess a less stable, disordered architecture.

Hsp104, an enzyme from yeast, breaks up both amyloid fibrils and disordered clumps. In the most recent issue of Cell, James Shorter, PhD, assistant professor of Biochemistry and Biophysics, and colleagues from the Perelman School of Medicine, University of Pennsylvania, show that Hsp104 switches mechanism to break up amyloid versus disordered clumps. For stable amyloid-type structures, Hsp104 needs all six of its subunits, which together make a hexamer, to pull the clumps apart. By contrast, for the more amorphous, non-amyloid clumps, Hsp104 required only one of its six subunits.

Test that can predict death - with a terrifying degree of accuracy

A blood test to determine how fast someone is ageing has been shown to work on a population of wild birds, the first time the ageing test has been used successfully on animals living outside a laboratory setting.

The test measures the average length of tiny structures on the tips of chromosomes called telomeres which are known to get shorter each time a cell divides during an organism’s lifetime.

Telomeres are believed to act like internal clocks by providing a more accurate estimate of a person’s true biological age rather than their actual chronological age.

This has led some experts to suggest that telomere tests could be used to estimate not only how fast someone is ageing, but possibly how long they have left to live if they die of natural causes.

Telomere tests have been widely used on experimental animals and at least one company is offering a £400 blood test in the UK for people interested in seeing how fast they are ageing based on their average telomere length.

Now scientists have performed telomere tests on an isolated population of songbirds living on an island in the Seychelles and found that the test does indeed accurately predict an animal’s likely lifespan.

“We saw that telomere length is a better indicator of life expectancy than chronological age. So by measuring telomere length we have a way of estimating the biological age of an individual – how much of its life it has used up,” said David Richardson of the University of East Anglia.

Great apes go through mid-life crisis

They may not take up surfing or start second careers as cupcake-makers, but chimpanzees and orangutans seem to go through a ‘mid-life crisis’, just like humans.

A study of 508 great apes in captivity shows that the animals’ sense of well-being bottoms out in their late 20s to mid-30s, the ape equivalent of middle age, before rebounding in old age.

The finding that mid-life crises may not be uniquely human suggests that the events might have a biological, rather than a sociological, cause.

Men and women worldwide, regardless of their wealth or status, experience a dip in happiness at middle-age, generally defined as from the mid-30s to late 50s. Despite this universality, social scientists have struggled to identify the underlying cause of the dissatisfaction. Social and economic factors, such as financial hardship and the failure to realize unrealistic ambitions, are possible causes.

Alexander Weiss, a psychologist at the University of Edinburgh, UK, and his team set out to see if there might be a biological factor involved in the crises. They sought to assess the well-being of captive chimpanzees and orangutans as judged by their keepers or those who knew them well.

The apes covered all age ranges, and their ‘happiness’ was rated through a survey answered by their keepers. The survey covered four criteria: the animals’ overall mood; how much pleasure they got out of socializing; their success in achieving goals such as obtaining food and objects they desire; and how happy the keeper would be if he or she were that animal for a week.

The survey is admittedly anthropomorphic, says Weiss, but he adds that it is easy for someone who spends a lot of time with an ape to gauge its mood. Moreover, his previous work shows that the measure of well-being is consistent when measured by different caretakers, and is based, in part, on inherited genetic factors.

Among three different groups of chimps and orangutans surveyed, the happiest tended to be the oldest and youngest, and the most dissatisfied tended to be in their 30s. The study, however, is a snapshot — it didn’t follow any of the apes over time — which means there could be confounding factors such as the early death of unhappy apes. Nonetheless, Weiss believes the results offer a true picture.

It Just Smells

If you play sounds of many different frequencies at the same time, they combine to produce neutral “white noise.” Neuroscientists say they have created an analogous generic scent by blending odors. Such “olfactory white” might rarely, if ever, be found in nature, but it could prove useful in research, other scientists say.

Using just a few hundred types of biochemical receptors, each of which respond to just a few odorants, the human nose can distinguish thousands of different odors. Yet humans can’t easily identify the individual components of a mixture, even when they can identify the odors alone, says Noam Sobel, a neuroscientist at the Weizmann Institute of Science in Rehovot, Israel. Now, he and his colleagues suggest, various blends made up of a large number of odors all begin to smell the same—even when the blends share no common components.

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Although many scents—such as coffee, wine, roses, and dirty socks—are complex blends containing hundreds of components, they are very distinctive. At least two factors are responsible, Sobel says: The individual odorants are often chemically related, and often one or more of them is vastly more intense than the rest.

The team’s findings are “a clever piece of work that shows the olfactory system works exactly as we would predict from our current understanding of it,” says Tim Jacob, a neuroscientist at Cardiff University in the United Kingdom. “That is, if you stimulate every olfactory ‘channel’ to the same extent, the brain cannot characterize or identify a particular smell,” he notes.

“Olfactory white is a neat idea, and it draws interesting parallels to white light and white noise,” says Jay Gottfried, an olfactory neuroscientist at Northwestern University’s Feinberg School of Medicine in Chicago, Illinois. The new study “definitely adds new information about how the brain interprets odors,” he notes.

Even though olfactory white is not likely to be encountered in nature, the concept could be useful, Gottfried says. “Researchers have found that white noise is a useful stimulus in experiments to probe auditory responses,” he notes, and scientists probing the human sense of smell might find similar uses for olfactory white.

The Hazards of Growing Up Painlessly

The girl who feels no pain was in the kitchen, stirring ramen noodles, when the spoon slipped from her hand and dropped into the pot of boiling water. It was a school night; the TV was on in the living room, and her mother was folding clothes on the couch. Without thinking, Ashlyn Blocker reached her right hand in to retrieve the spoon, then took her hand out of the water and stood looking at it under the oven light. She walked a few steps to the sink and ran cold water over all her faded white scars, then called to her mother, “I just put my fingers in!” Her mother, Tara Blocker, dropped the clothes and rushed to her daughter’s side. “Oh, my lord!” she said — after 13 years, that same old fear — and then she got some ice and gently pressed it against her daughter’s hand, relieved that the burn wasn’t worse.

“I showed her how to get another utensil and fish the spoon out,” Tara said with a weary laugh when she recounted the story to me two months later. “Another thing,” she said, “she’s starting to use flat irons for her hair, and those things get superhot.”

Tara was sitting on the couch in a T-shirt printed with the words “Camp Painless But Hopeful.” Ashlyn was curled on the living-room carpet crocheting a purse from one of the skeins of yarn she keeps piled in her room. Her 10-year-old sister, Tristen, was in the leather recliner, asleep on top of their father, John Blocker, who stretched out there after work and was slowly falling asleep, too. The house smelled of the homemade macaroni and cheese they were going to have for dinner. A South Georgia rainstorm drummed the gutters, and lightning illuminated the batting cage and the pool in the backyard.

Without lifting her eyes from the crochet hooks in her hands, Ashlyn spoke up to add one detail to her mother’s story. “I was just thinking, What did I just do?” she said.

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A 3-D Light Switch for the Brain

A new tool for neuroscientists delivers a thousand pinpricks of light to a chunk of gray matter smaller than a sugar cube. The new fiber-optic device, created by biologists and engineers at the Massachusetts Institute of Technology (MIT) in Cambridge, is the first tool that can deliver precise points of light to a 3-D section of living brain tissue. The work is a step forward for a relatively new but promising technique that uses gene therapy to turn individual brain cells on and off with light.

Scientists can use the new 3-D “light switch” to better understand how the brain works. It might also be used one day to create neural prostheses that could treat conditions such as Parkinson’s disease and epilepsy. The researchers describe their device in a paper published today in the Optical Society’s (OSA) journal Optics Letters.

The technique of manipulating neurons with light is only a few years old, but the authors estimate that thousands of scientists are already using this technology, called optogenetics, to study the brain. In optogenetics, researchers first sensitize select cells in the brain to a particular color of light. Then, by illuminating precise areas of the brain, they are able to selectively activate or deactivate the individual neurons that have been sensitized.

Ed Boyden, a synthetic biologist at MIT and co-lead researcher on the paper, is a pioneer of this emerging field, which he says offers the ability to probe connections in the brain.

"You can see neural activity in the brain that is associated with specific behaviors," Boyden says, “but is it important? Or is it a passive copy of important activity located elsewhere in the brain? There’s no way to know for sure if you just watch.” Optogenetics allows scientists to play a more active role in probing the brain’s connections, to fire up one type of cell or deactivate another and then observe the effect on a behavior, such as quieting a seizure.

Unlike the previous, 1-D versions of this light-emitting device, the new tool delivers light to the brain in three dimensions, opening the potential to explore entire circuits within the brain. So far, the 3-D version has been tested in mice, although Boyden and colleagues have used earlier optogenetic technologies with non-human primates as well.

HEARBO Robot Has Superhearing

We live in a world of sounds, full of beautiful music, birds chirping, and the voices of our friends. It’s a rich cacophony, with blaring beeps, accented alarms, and knock-knock jokes. The sound of a door opening can alert us to a friend’s arrival, and a door slamming can alert us to an impending argument.

HEARBO (HEAR-ing roBOt) is a robot developed at Honda Research Institute–Japan (HRI-JP), and its job is to understand this world of sound, in a field called Computational Auditory Scene Analysis.