There was no association between levels of vitamin D in newborn babies and the risk of developing multiple sclerosis in adulthood. This is the observation made by researchers at Karolinska Institutet in a newly published study. The hypothesis could be tested with the help of the unique biobanks available in Sweden and at KI.
Multiple sclerosis (MS) is a chronic disease that affects the central nervous system, i.e., the brain and the spinal cord. Approximately 17,000 people in Sweden suffer from MS with the disease causing inflammations and lesions on the nerve fibres, preventing impulses from being received as they should be.
One hypothesis that has been widely discussed in recent years is on the link between low vitamin D levels in newborn babies and the risk of developing MS in adulthood. This hypothesis is based, amongst other things, on studies that have shown that those born in the spring have an increased risk of suffering from the disease when compared to those born in the autumn. The theory is that low vitamin D levels resulting from limited sun exposure during pregnancy increase the risk of MS in children born after the winter.
For the first time, researchers at Karolinska Institutet have been able to test this hypothesis which until now has only been assessed by indirect observations. Vitamin D levels at the birth of MS sufferers were measured and compared with those of control persons. The results have been published in the journal Annals of Neurology.
“We could not see any association between levels of vitamin D at birth and risk of MS in adulthood,” says Peter Ueda, researcher at the Department of Clinical Neuroscience and one of the researchers behind the study led by Tomas Olsson, Professor of Neurology at the same department and Lars Alfredsson, Professor at the Institute of Environmental Medicine.
“However a weaker link cannot be ruled out, nor can the link be ruled out for people with certain genes.”
“There are several reasons why the link between vitamin D at birth and later risk of MS has not been directly assessed previously,” explains Peter Ueda. As MS is a relatively uncommon disease, access to an entire population’s worth of blood samples that have been stored since birth would be required in order to provide reliable results. It must also be possible to trace the blood samples, preferably more than 30 years back in time– as this is the age around which the disease develop.
“Such biobanks are uncommon, however one can be found in Sweden. This study could be conducted due to the unique possibilities for monitoring and follow-up of patients in Sweden,” he says.
The study included 459 participants with MS and 663 healthy control participants. The participants were gathered from the EIMS project led by the Institute of Environmental Medicine at Karolinska Institutet in collaboration with neurology departments at hospitals in all Swedish counties. Each patient diagnosed with MS – in addition to control persons matched based on sex, age and place of residence – was asked to provide a blood sample and answer a questionnaire. The information is then saved and used for studies on the factors that cause MS.
Vitamin D levels from the time of birth of MS patients and their respective controls were determined with the help of the PKU register which contains blood samples from newborn Swedish people from 1975 onwards. For measuring vitamin D levels (25-hydroxy vitamin D) in dried blood samples, a a method developed by researchers at the University of Queensland, Australia was used.
Peter Ueda explains how results from the previously mentioned month of birth studies, that identified how those born in the spring had an increased risk of MS, had hinted of a potential opportunity to prevent a significant number of MS cases by ensuring that vitamin D levels in pregnant women are not too low.
“However, our results do not support the hypothesis of such a possibility for reducing MS risk,” he explains.
The lack of a link between vitamin D levels in newborns and the risk for MS remained, even when the researchers took into account certain factors that could affect the results – for example, month of birth, and the geographical latitude of birth, in as well as sun exposure and intake of vitamin D in adult age.
(Image: Helen Traherne)
Aggregates of the Huntington’s disease-associated protein, huntingtin, can spread among neurons, according to a study published last month in Nature Neuroscience, giving credence, experts suggest, to the idea that the propagation of mutant proteins may be a unifying feature of neurodegenerative diseases.
Huntington’s disease, a progressive neurodegenerative disorder that impairs both movement and cognition, is caused by dominant mutations in the huntingtin gene that lead to abnormally long stretches of the amino acid glutamine in the huntingtin protein. These proteins tend to clump in affected neurons, although whether the aggregates are a cause of neurodegeneration or perhaps some kind of cellular response to the mutant protein is still a matter of debate.
The huntingtin gene is expressed throughout the nervous system, so it is hard to tell whether huntingtin aggregates originate within the cells in which they are observed.
To answer this question, researchers from the Novartis Institutes for Biomedical Research in Basel, Switzerland, and their academic colleagues introduced neurons with the wild-type huntingtin gene into mutant brain tissue—both in cell culture and in a mouse model. After several weeks, they observed that aggregates of mutant huntingtin protein had appeared in the wild-type neurons, indicating that the protein from the mutant neurons had spread.
“This paper reports for the first time that mutant huntingtin can spread between neurons,” lead author F. Paolo Di Giorgio, who studies Huntington’s and other neurodegenerative diseases at the Novartis Institutes, told The Scientist.
Neurodegenerative diseases including Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration have been shown to involve the propagation of aggregate pathology from cell to cell. Evidence is mounting that neurodegenerative diseases share mechanisms with prion diseases—exemplified by mad cow disease and its human counterpart, Creutzfeldt-Jakob disease, in which misfolded, deleterious proteins propagate over long distances and cause other molecules to misfold.
“This is the first time that diseases involving what are called polyglutamine-expanded proteins have been found to involve a process of transneuronal propagation,” said Albert La Spada, who studies neurodegenerative disease at the University of California, San Diego, School of Medicine and penned a companion article about the study but was not involved in the work. Polyglutamine expansion is a feature of eight neurodegenerative diseases, including Huntington’s, La Spada said. “That’s significant because it extends the scope of this mechanism more broadly across potentially all neurodegenerative diseases. That’s what makes this study particularly exciting.”
To see if huntingtin aggregates could propagate, the researchers first grew human embryonic stem cells alongside brain slices from either mice with a Huntington’s-like disease or wild-type mice. The stem cells differentiated into neurons and formed connections with the mutant neurons of the brain slices. By six weeks of this co-culture, the introduced wild-type neurons exhibited mutant huntingtin aggregates. They also had shorter and fewer appendages than did neurons co-cultured with wild-type brain slices. Further, introduced neurons that exhibited huntingtin aggregates had significantly narrower cell bodies and fewer projections than those that did not.
“Cells that bear these aggregates show abnormal pathology that is more pronounced [with] respect to cells that don’t bear the aggregates,” said Di Giorgio, “so it seems that when the neurons uptake mutant huntingtin—wild-type neurons that don’t carry any mutation—they will start to show signs of cellular atrophy.”
Huntington’s disease typically begins in the striatum, a brain region involved in movement control, and progresses to the cortex. To examine the way Huntington’s disease might affect this neuronal pathway, the researchers co-cultured striatal and cortical brain slices from wild-type and mutant mice. They found that when mutant cortical neurons and wild-type striatal brain slices were cultured together, functional neuronal connections formed between the brain slices, and mutant huntingtin spread to the wild-type neurons.
When researchers tried the reverse approach—linking mutant striatum and wild-type cortex—the two regions did not form neuronal connections, suggesting that mutant huntingtin within the striatum could disrupt corticostriatal connections.
To explore the corticostriatal pathway in vivo, the researchers used a virus to introduce the polyglutamine-repeat-encoding part of the huntingtin gene into the cortical neurons of wild-type mice. The neurons that were infected with the virus developed aggregates as expected, as did the striatal neurons with which the infected cells made connections.
Finally, in order to probe the mechanism of mutant huntingtin spreading, the researchers returned to their original experimental setup—co-cultures of wild-type human neurons and mutant mouse brain slices—and inhibited the synaptic vesicle pathway using botulinum toxin. Blocking the synaptic transmission reduced the spread of the huntingtin aggregates.
Taken together, these results lend support to the idea that Huntington’s disease shares features with other neurodegenerative diseases, and with prion diseases.
“If neurodegenerative diseases have a unifying feature,” neurobehavioral geneticist X. William Yang from the University of California, Los Angeles, told The Scientist in an e-mail, “then understand[ing] the mechanisms or developing therapies against such common features may have more general implications/utility for all such disorders.”
“If spreading occurs and drives disease progression, then blocking the spreading process could be a viable treatment approach,” added La Spada. “If the spreading process occurs extracellularly … then immunizing patients against a disease protein could be explored as a therapy.”
In a long-term, large-scale population-based study of individuals aged 55 years or older in the general population researchers found that those diagnosed with mild cognitive impairment (MCI) had a four-fold increased risk of developing dementia or Alzheimer’s disease (AD) compared to cognitively…
Researchers from The University of Western Australia have shown that electromagnetic stimulation can alter brain organisation which may make your brain work better.
In results from a study published today in the prestigious Journal of Neuroscience, researchers from The University of Western…
Fear in a mouse brain looks much the same as fear in a human brain.
When a frightening stimulus is encountered, the thalamus shoots a message to the amygdala — the primitive part of the brain — even before it informs the parts responsible for higher cognition. The amygdala then goes into its hard-wired fight-or-flight response, triggering a host of predictable symptoms, including racing heart, heavy breathing, startle response, and sweating.
The similarities of fear response in the brains of mice and men have allowed scientists to understand the neural circuitry and molecular processes of fear and fear behaviors perhaps better than any other response. That understanding has spurred breakthroughs in treatments for psychiatric disorders that are underpinned by fear.
Anxiety disorders are one of the most common mental illnesses in the country, with nearly one-third of Americans experiencing symptoms at least once during their lives. There are generalized anxiety disorders and fear-related disorders, which include panic disorders, phobias, and post-traumatic stress disorder (PTSD).
Emory psychiatrist and researcher Kerry Ressler is on the front lines of fear-disorder research. In his lab at Yerkes National Primate Research Center, he studies the molecular and cellular mechanisms of fear learning and extinction in mouse models. At Grady Memorial Hospital, he investigates the psychology, genetics, and biology of PTSD. And through the Grady Trauma Project, he works to draw attention to the problem of inner city intergenerational violence.
"If you look at Kerry’s work, it can seem like it’s all over the place — he’s got so many studies going on, and he collaborates with so many other scientists," says Barbara Rothbaum, associate vice chair of clinical research in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory. "But they are all pieces to the same puzzle. All his work, from molecular to clinical to policy, fits together and starts telling a story." A Howard Hughes Medical Institute investigator, Ressler was recently elected to the Institute of Medicine — one of the highest honors in the fields of health and medicine. He was named a member of a new national PTSD consortium led by Draper Laboratory. And he recently appeared on the Charlie Rose show’s brain series.
Panic attacks seem to tie the fear-related disorders together, he explained on Charlie Rose. Everyone experiences fear, which evolved as a survival mechanism, but it only rises to a clinical level when people are unable to function normally in the face of it. For instance, PTSD includes not only intrusive thoughts, memories, nightmares, and startle responses, but also the concept of avoidance, which may extend to other areas of the individual’s life.
"There’s a patient I’ve seen who was attacked in a dark alley," Ressler shared on the show. "Initially it just felt dangerous to go out at night, but after a while she grew afraid of men and couldn’t go to that part of town. Then she couldn’t leave her house, and finally, her bedroom. The world got more and more dangerous."
The ultimate comeback: Bringing the dead back to life
A radical procedure that involves replacing a patients’ blood with cold salt water could retrieve people from the brink of death, says David Robson.
“When you are at 10C, with no brain activity, no heartbeat, no blood – everyone would agree that you’re dead,” says Peter Rhee at the University of Arizona, Tucson. “But we can still bring you back.”
Should Humanity Try to Contact Intelligent Aliens?
Astronomers have detected nearly 2,000 alien planets to date. As that number continues to rise, so too does the prospect of finding intelligent extraterrestrial life.
In terms of the search for extraterrestrial intelligence (SETI), it may no longer be a matter of answering the “are we alone” question, some scientists say. Rather, just how crowded is the universe?
Supermassive black hole blows molecular gas out of a galaxy at 1 million kilometres per hour
- Long-held mystery surrounding the evolution of galaxies solved by academics at the University of Sheffield
- Findings deepen our understanding of the future of our own galaxy, which will collide with Andromeda in 5 billion years
New research by academics at the University of Sheffield has solved a long-standing mystery surrounding the evolution of galaxies, deepening our understanding of the future of the Milky Way.
The supermassive black holes in the cores of some galaxies drive massive outflows of molecular hydrogen gas. As a result, most of the cold gas is expelled from the galaxies. Since cold gas is required to form new stars, this directly affects the galaxies’ evolution.
Scientists Criticize Europe’s $1.6B Brain Project
Dozens of neuroscientists are protesting Europe’s $1.6 billion attempt to recreate the functioning of the human brain on supercomputers, fearing it will waste vast amounts of money and harm neuroscience in general.
The 10-year Human Brain Project is largely funded by the European Union. In an open letter issued Monday, more than 190 neuroscience researchers called on the EU to put less money into the effort to “build” a brain, and to invest instead in existing projects.
If the EU doesn’t adopt their recommendations, the scientists said, they will boycott the Human Brain Project and urge colleagues to do the same.
If you rub your closed eyes, you’ll “see” a virtual rainbow of colors, shapes, squiggles, and lines. Those are called phosphenes, and the eye and the brain work together to create these weird little visual blips.
Phosphenes occur when there is no external visual stimulus. That can happen when you close your eyes or when you’re focused on scenery with little to no input as to depth or changes, such as a dark highway at night.
People who spend long periods of time in sensory deprivation or meditation often report seeing visions, which can be chalked up to the appearance of phosphenes.
The presence of physical stimulus to the eye, like pushing on the eyeball, will create temporary phosphenes, and more traumatic events like head injuries can create permanent squiggles.
In these cases, phosphenes are present because the visual centers of the brain are active without the presence of external visual stimuli.
For example, when conscious patients undergoing brain surgery had different areas of their brains electrically stimulated, they reported seeing phosophenes.
In studies of blind people, it’s been found that the appearance of phosphenes happens in different areas along the sight pathway between the eye and the brain, depending on what part of the visual system has been damaged.
Humans aren’t the only ones who can see these dancing bits of light and color—the phenomenon has been observed in animals as well.
Short Sleep, Aging Brain
Researchers at Duke-NUS Graduate Medical School Singapore (Duke-NUS) have found evidence that the less older adults sleep, the faster their brains age. These findings, relevant in the context of Singapore’s rapidly ageing society, pave the way for future work on sleep loss and its contribution to cognitive decline, including dementia.
Past research has examined the impact of sleep duration on cognitive functions in older adults. Though faster brain ventricle enlargement is a marker for cognitive decline and the development of neurodegenerative diseases such as Alzheimer’s, the effects of sleep on this marker have never been measured.
Master Switch for Myelination in Human Brain Stem Cells is Identified
Finding is key to developing MS treatments using stem cells.
Scientists at the University at Buffalo have identified the single transcription factor or “master switch” that initiates the critical myelination process in the brain. Funded by New York Stem Cell Science, the research will be published online in Proceedings of the National Academy of Sciences (PNAS) on June 30.
The identification of this factor, SOX10, in human brain cells, brings researchers closer to the goal of treating multiple sclerosis (MS) by transplanting into patients the brain cells that make myelin.