Posts tagged brain development
Articles and news from the latest research reports.
Study finds higher levels of several toxic metals in children with autism
In a recently published study in the journal Biological Trace Element Research, Arizona State University researchers report that children with autism had higher levels of several toxic metals in their blood and urine compared to typical children. The study involved 55 children with autism ages 5–16 years compared to 44 controls of similar age and gender.
The autism group had significantly higher levels of lead in their red blood cells (+41 percent) and significantly higher urinary levels of lead (+74 percent), thallium (+77 percent), tin (+115 percent), and tungsten (+44 percent). Lead, thallium, tin, and tungsten are toxic metals that can impair brain development and function, and also interfere with the normal functioning of other body organs and systems.
A statistical analysis was conducted to determine if the levels of toxic metals were associated with autism severity, using three different scales of autism severity. It was found that 38-47 percent of the variation of autism severity was associated with the level of several toxic metals, with cadmium and mercury being the most strongly associated.
In the paper about the study, the authors state “We hypothesize that reducing early exposure to toxic metals may help ameliorate symptoms of autism, and treatment to remove toxic metals may reduce symptoms of autism; these hypotheses need further exploration, as there is a growing body of research to support it.”
The study was led by James Adams, a President’s Professor in the School for Engineering of Matter, Transport and Energy, one of ASU’s Ira A. Fulton Schools of Engineering. He directs the ASU Autism/Asperger’s Research Program.
Adams previously published a study on the use of DMSA, an FDA-approved medication for removing toxic metals. The open-label study found that DMSA was generally safe and effective at removing some toxic metals. It also found that DMSA therapy improved some symptoms of autism. The biggest improvement was for children with the highest levels of toxic metals in their urine.
Overall, children with autism have higher average levels of several toxic metals, and levels of several toxic metals are strongly associated with variations in the severity of autism for all three of the autism severity scales investigated.
(Source: fullcircle.asu.edu)
First snaps made of fetal brains wiring themselves up
The first images have been captured of the fetal brain at different stages of its development. The work gives a glimpse of how the brain’s neural connections form in the womb, and could one day lead to prenatal diagnosis and treatment of conditions such as autism and schizophrenia.
We know little about how the fetal brain grows and functions – not only because it is so small, says Moriah Thomason of Wayne State University in Detroit, but also because “a fetus is doing backflips as we scan it”, making it tricky to get a usable result.
Undeterred, Thomason’s team made a series of functional magnetic resonance imaging (fMRI) scans of the brains of 25 fetuses between 24 and 38 weeks old. Each scan lasted just over 10 minutes, and the team kept only the images taken when the fetus was relatively still.
The researchers used the scans to look at two well-understood features of the developing brain: the spacing of neural connections and the time at which they developed. As expected, the two halves of the fetal brain formed denser and more numerous connections between themselves from one week to the next. The earliest connections tended appear in the middle of the brain and spread outward as the brain continued to develop.
Thomason says that the team is now scanning up to 100 fetuses at different stages of development. These scans might allow them to start to see variation between individuals. They are also applying algorithms to the scanning program that will help correct for the fetus’s movements, so fewer scans will be needed in future.
Once they understand what a normal fetal brain looks like, the researchers hope to study brains that are forming abnormal connections. Disorders such as schizophrenia or autism, for instance, are believed to start during development and might be due to faulty brain connections. Understanding the patterns that characterise these diseases might one day allow physicians to spot early warning signs and intervene sooner. Just as importantly, such images might improve our understanding of how these conditions develop in the first place, Thomason says.
Emi Takahashi of Boston Children’s Hospital says that one way to do this would be to follow a large group of children after they are born, and look back at the prenatal scans of those who later develop a brain disorder. Although she says the study is a very good first step, understanding the miswiring of the brain is so difficult that it may be some time before the results of such work become useful in clinical settings.
(Source: newscientist.com)
Clues to Fetal Alcohol Risk: Molecular switch promises new targets for diagnosis and therapy
Fetal alcohol syndrome is the leading preventable cause of developmental disorders in developed countries. And fetal alcohol spectrum disorder (FASD), a range of alcohol-related birth defects that includes fetal alcohol syndrome, is thought to affect as many as 1 in 100 children born in the United States.
Any amount of alcohol consumed by the mother during pregnancy poses a risk of FASD, a condition that can include the distinct pattern of facial features and growth retardation associated with fetal alcohol syndrome as well as intellectual disabilities, speech and language delays, and poor social skills. But drinking can have radically different outcomes for different women and their babies. While twin studies have suggested a genetic component to susceptibility to FASD, researchers have had little success identifying who is at greatest risk or what genes are at play.
Research from Harvard Medical School and Veterans Affairs Boston Healthcare System sheds new light on this question, identifying for the first time a signaling pathway that might determine genetic susceptibility for the development of FASD. The study was published online Feb. 19 in the journal Proceedings of the National Academy of Sciences.
“Our work points to candidate genes for FASD susceptibility and identifies a path for the rational development of drugs that prevent ethanol neurotoxicity,” said Michael Charness, chief of staff at VA Boston Healthcare System and HMS professor of neurology. “And importantly, identifying those mothers whose fetuses are most at risk could help providers better target intensive efforts at reducing drinking during pregnancy.”
The discovery also solves a riddle that had intrigued Charness and other researchers for nearly two decades. In 1996, Charness and colleagues discovered that alcohol disrupted the work of a human protein critical to fetal neural development—a major clue to the biological processes of FASD. The protein, L1, projects through the surface of a cell to help it adhere to its neighbors. When Charness and his team introduced the protein to a culture of mouse fibroblasts cells, L1 increased cell adhesion. Tellingly, the effect was erased in the presence of ethanol (beverage alcohol).
Charness and his team went on to develop multiple cell lines from that first culture, and that’s where they encountered the riddle: In some of those lines, alcohol disrupted L1’s adhesive effect, while in others it did not.
“How could it be possible that a cell that expresses L1 is completely sensitive to alcohol, and others that express it are completely insensitive?” asked Charness, who is also faculty associate dean for veterans hospital programs at HMS and assistant dean at Boston University School of Medicine.
Clearly, something else was affecting the protein’s sensitivity to alcohol — but what? Studies of twins provided one clue: Identical twins are more likely than fraternal twins to have the same diagnosis, positive or negative, for FASD. “That concordance suggests that there are modifying genes, susceptibility genes, that predispose to this condition,” Charness said.
Shedding New Light on Infant Brain Development
A new study by Columbia Engineering researchers finds that the infant brain does not control its blood flow in the same way as the adult brain. The findings, which the scientists say could change the way researchers study brain development in infants and children, are published in the February 18 Early Online edition of Proceedings of the National Academy of Sciences (PNAS).
“The control of blood flow in the brain is very important,” says Elizabeth Hillman, associate professor of biomedical engineering and of radiology, who led the research study in her Laboratory for Functional Optical Imaging at Columbia. “Not only are regionally specific increases in blood flow necessary for normal brain function, but these blood-flow increases form the basis of signals measured in fMRI, a critical imaging tool used widely in adults and children to assess brain function. Many prior fMRI studies have overlooked the possibility that the infant brain controls blood flow differently.”
“Our results are fascinating,” says Mariel Kozberg, a neurobiology MD-PhD candidate who works under Hillman and is the lead author of the PNAS paper. “We found that the immature brain does not generate localized blood-flow increases in response to stimuli. By tracking changes in blood-flow control with increasing age, we observed the brain gradually developing its ability to increase local blood flow and, by adulthood, generate a large blood-flow response.”
The study results suggest that fMRI experiments in infants and children should be carefully designed to ensure that maturation of blood-flow control can be delineated from changes in neuronal development. “On the other hand,” says Hillman, “our findings also suggest that vascular development may be an important new factor to consider in normal and abnormal brain development, so our findings could represent new markers of normal and abnormal brain development that could potentially be related to a range of neurological or even psychological conditions.”
Brain plasticity
Babies’ brains are highly plastic, meaning they’re constantly adapting as they learn and respond to the world and people around them.
Daphne Maurer, director of the Visual Development Laboratory at McMaster University in Hamilton, Ontario, has found clues as to when plasticity might be locked off in babies and how in some adults it actually may persist unbeknown to them.
Early music lessons boost brain development
If you started piano lessons in grade one, or played the recorder in kindergarten, thank your parents and teachers. Those lessons you dreaded – or loved – helped develop your brain. The younger you started music lessons, the stronger the connections in your brain.
A study published last month in the Journal of Neuroscience suggests that musical training before the age of seven has a significant effect on the development of the brain, showing that those who began early had stronger connections between motor regions – the parts of the brain that help you plan and carry out movements.
This research was carried out by students in the laboratory of Concordia University psychology professor Virginia Penhune, and in collaboration with Robert J. Zatorre, a researcher at the Montreal Neurological Institute and Hospital at McGill University.
The study provides strong evidence that the years between ages six and eight are a “sensitive period” when musical training interacts with normal brain development to produce long-lasting changes in motor abilities and brain structure. “Learning to play an instrument requires coordination between hands and with visual or auditory stimuli,” says Penhune. “Practicing an instrument before age seven likely boosts the normal maturation of connections between motor and sensory regions of the brain, creating a framework upon which ongoing training can build.”
Abnormal Brain Development in Fetuses of Obese Women
In a study to be presented on February 15 between 8 a.m. and 10 a.m. PST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in San Francisco, California, researchers from Tufts Medical Center will present findings showing the effects of maternal obesity on a fetus, specifically in the development of the brain.
The study, conducted at the Mother Infant Research Institute (MIRI) at Tufts Medical Center in Boston, Mass., looked at the fetal development of 16 pregnant women, eight obese and eight lean, to see what effects maternal obesity had on fetal gene expression. Researchers have found that fetuses of obese women had differences in gene expression as early as the second trimester, compared to fetuses of women who were a healthy weight. Of particular note were patterns of gene expression suggestive of abnormal brain development in fetuses of obese women.
During gestation, fetuses go through apoptosis, a developmental process of programmed cell death. However, fetuses of the obese women were observed to have decreased apoptosis, which is an important part of normal fetal neurodevelopment. Dr. Diana Bianchi, senior author of the study and executive director of MIRI, describes apoptosis as a pruning process, clearing out space for new growth.
“Women won’t be surprised to hear being obese while pregnant can lead to obesity in the child,” said Dr. Andrea Edlow, lead author of the study and fellow in Maternal-Fetal Medicine at Tufts Medical Center. “But what might surprise them is the potential effect it has on the brain development of their unborn child.”
It is too early to know the implications of their findings, but maternal obesity is a rapidly growing problem in the U.S., with one in three women being obese at conception. The conclusion of the study points to the role of gene expression studies such as this one in helping elucidate possible mechanisms for recently-described postnatal neurodevelopmental abnormalities in children of obese women, including increased rates of autism and altered hypothalamic appetite regulation.
Genes for autism and schizophrenia only active in developing brains
Genes linked to autism and schizophrenia are only switched on during the early stages of brain development, according to a collaboration between researchers at Imperial College London, the University of Oxford and King’s College London.
This new study adds to the evidence that autism and schizophrenia are neurodevelopmental disorders, a term describing conditions that originate during early brain development.
The researchers studied gene expression in the brains of mice throughout their development, from 15-day old embryos to adults, and their results are published in Proceedings of the National Academy of Sciences.
The research focused on cells in the ‘subplate’, a region of the brain where the first neurons (nerve cells) develop. Subplate neurons are essential to brain development, and provide the earliest connections within the brain.
'The subplate provides the scaffolding required for a brain to grow, so is important to consider when studying brain development,' says Professor Zoltán Molnár, senior author of the paper from the University of Oxford, 'Looking at the pyramids in Egypt today doesn't tell us how they were actually built. Studying adult brains is like looking at the pyramids today, but by studying the developing brains we are able to see the transient scaffolding that has been used to construct it.'
The study shows that certain genes linked to autism and schizophrenia are only active in the subplate during specific stages of development. The data analysis was designed by Dr Enrico Petretto, Senior Lecturer in Genomic Medicine at Imperial College London. Dr Petretto said: “We looked at the full network of genes in the brain to identify which pathways play a role in early brain development. This allowed us to find coherent clusters of genes previously associated with susceptibility to autism spectrum disorders or schizophrenia. These results provide a unique resource for our understanding of how gene behaviour changes in the mouse subplate from the early embryonic stage to adulthood. This means we are better equipped to investigate how the gene network changes in the developing brain and identify any links with neurodevelopmental disorders.”
The team was able to map gene activity in full detail thanks to these new methods which allowed them to dissect and profile gene expression from small numbers of cells. This also enabled them to identify the different populations of subplate neurons more accurately.
Professor Hugh Perry, chair of the Medical Research Council’s Neuroscience and Mental Health Board, said: “By being able to pinpoint common genetic factors for neurological conditions such as autism and schizophrenia, scientists are able to understand an important part of the story as to why things go awry as our brains develop. The Medical Research Council’s commitment to a broad portfolio of neuroscience and mental health research places us in a unique position to respond to the challenge of mental ill health and its relationship with physical health and wellbeing.”
(Source: www3.imperial.ac.uk)
Scientists learn more about how inhibitory brain cells get excited
Scientists have found an early step in how the brain’s inhibitory cells get excited. A natural balance of excitement and inhibition keeps the brain from firing electrical impulses randomly and excessively, resulting in problems such as schizophrenia and seizures. However excitement is required to put on the brakes.
“When the inhibitory neuron is excited, its job is to suppress whatever activity it touches,” said Dr. Lin Mei, Director of the Institute of Molecular Medicine and Genetics at the Medical College of Georgia at Georgia Regents University and corresponding author of the study in Nature Neuroscience.
Mei and his colleagues found that the protein erbin, crucial to brain development, is critical to the excitement.
Chance finding reveals new control on blood vessels in developing brain
Zhen Huang freely admits he was not interested in blood vessels four years ago when he was studying brain development in a fetal mouse.
Instead, he wanted to see how changing a particular gene in brain cells called glia would affect the growth of neurons.
The result was hemorrhage, caused by deteriorating veins and arteries, and it begged for explanation.
"It was a surprising finding," says Huang, an assistant professor of neuroscience and neurology at the University of Wisconsin-Madison. "I was mainly interested in the neurological aspect, how the brain develops and wires itself to prepare for all the wonderful things it does."
But chance favors the prepared mind, as Louis Pasteur said, and Huang knew he needed to follow up on the suggestion that glia, normally considered “helpers” for the neurons, would affect the growth of blood vessels. For one thing, blood flow is a big deal in the brain, says Huang, whose collaborators included Shang Ma, in the graduate program in cellular and molecular biology at UW-Madison. “We know the brain is very energy-intensive. Per unit of volume, it consumes 10 times as much oxygen as the rest of the body.”
Although it makes intuitive sense that blood vessel development should be guided by neuronal development in some fashion, Huang spent years making sure he wasn’t being mislead by his experiment. Now, he’s satisfied himself, and his scientific reviewers, and the journal PLOS Biology has just published his study.