Posts tagged brain development
Articles and news from the latest research reports.
MR Spectroscopy Shows Differences in Brains of Preterm Infants
Premature birth appears to trigger developmental processes in the white matter of the brain that could put children at higher risk of problems later in life, according to a study being presented next week at the annual meeting of the Radiological Society of North America (RSNA).
Preterm infants—generally those born 23 to 36 weeks after conception, as opposed to the normal 37- to 42-week gestation—face an increased risk of behavioral problems, ranging from impulsiveness and distractibility to more serious conditions like autism and attention deficit hyperactivity disorder (ADHD).
"In the United States, we have approximately 500,000 preterm births a year," said Stefan Blüml, Ph.D., director of the New Imaging Technology Lab at Children’s Hospital Los Angeles and associate professor of research radiology at the University of Southern California in Los Angeles. "About 60,000 of these babies are at high risk for significant long-term problems, which means that this is a significant problem with enormous costs."
Dr. Blüml and colleagues have been studying preterm infants to learn more about how premature birth might cause changes in brain structure that may be associated with clinical problems observed later in life. Much of the focus has been on the brain’s white matter, which transmits signals and enables communication between different parts of the brain. While some white matter damage is readily apparent on structural magnetic resonance imaging (MRI), Dr. Blüml’s group has been using magnetic resonance spectroscopy (MRS) to look at differences on a microscopic level.
In this study, the researchers compared the concentrations of certain chemicals associated with mature white matter and gray matter in 51 full-term and 30 preterm infants. The study group had normal structural MRI findings, but MRS results showed significant differences in the biochemical maturation of white matter between the term and preterm infants, suggesting a disruption in the timing and synchronization of white and gray matter maturation. Gray matter is the part of the brain that processes and sends out signals.
"The road map of brain development is disturbed in these premature kids," Dr. Blüml said. "White matter development had an early start and was ‘out of sync’ with gray matter development."
This false start in white matter development is triggered by events after birth, according to Dr. Blüml.
"This timeline of events might be disturbed in premature kids because there are significant physiological switches at birth, as well as stimulatory events, that happen irrespective of gestational maturity of the newborn," he said. "The most apparent change is the amount of oxygen that is carried by the blood."
Dr. Blüml said that the amount of oxygen delivered to the fetus’s developing brain in utero is quite low, and our brains have evolved to optimize development in that low oxygen environment. However, when infants are born, they are quickly exposed to a much more oxygen-rich environment.
"This change may be something premature brains are not ready for," he said.
While this change may cause irregularities in white matter development, Dr. Blüml noted that the newborn brain has a remarkable capacity to adapt or even “re-wire” itself—a concept known as plasticity. Plasticity not only allows the brain to govern new skills over the course of development, like learning to walk and read, but could also make the brains of preterm infants and young children more responsive to therapeutic interventions, particularly if any abnormalities are identified early.
"Our research points to the need to better understand the impact of prematurity on the timing of critical maturational processes and to develop therapies aimed at regulating brain development," Dr. Blüml said.
(Source: www2.rsna.org)
Meat, egg and dairy nutrient essential for brain development
Asparagine, found in foods such as meat, eggs, and dairy products, was until now considered non-essential because it is produced naturally by the body. Researchers at the University of Montreal and its affiliated CHU Sainte-Justine Hospital found that the amino acid is essential for normal brain development. This is not the case for other organs. “The cells of the body can do without it because they use asparagine provided through diet. Asparagine, however, is not well transported to the brain via the blood-brain barrier,” said senior co-author of the study Dr. Jacques Michaud, who found that brain cells depend on the local synthesis of asparagine to function properly. First co-author José-Mario Capo-Chichi and colleague Grant Mitchell also made major contributions to the study.
In April 2009, a Quebec family experienced the worst tragedy for parents: before the age of one, one of their sons died of a rare genetic disease causing congenital microcephaly, intellectual disability, cerebral atrophy, and refractory seizures. The event was even more tragic because it was the third infant to die in this family from the same disease.
This tragedy led Dr. Michaud to discover the genetic abnormality responsible for this developmental disorder. “We are not at the verge of a miracle drug,” Michaud said, “but we at least know where to look.”
The team identified the gene affected by the mutation code for asparagine synthetase, the enzyme responsible for synthesizing the amino acid asparagine. The study is the first to associate a specific genetic variant with a deficiency of this enzyme. “In healthy subjects, it seems that the level of asparagine synthetase in the brain is sufficient to supply neurons,” Michaud said. “In individuals with the disability, the enzyme is not produced in sufficient quantity, and the resulting asparagine depletion affects the proliferation and survival of cells during brain development.”
Potential treatment
Children who are carriers of this mutation suffer, to varying degrees, from a variety of symptoms, including intellectual disability and cerebral atrophy, which can lead to death. The Quebec family lost three infant sons to this disorder. Two of their other children are alive and healthy.
Knowledge about gene mutations can be used to develop treatments. “Our results not only open the door to a better understanding of the disease,” Michaud said, “but they also give us valuable information about the molecular mechanisms involved in brain development, which is important for the development of new treatments.”
For example, asparagine supplement could be given to infants to ensure an adequate level of asparagine in the brain and the latter’s normal development. “The amount of supplementation remains to be determined, as well as its effectiveness,” said the geneticist. “Since these children are already born with neurological abnormalities, it is uncertain whether this supplementation would correct the neurological deficits.”
Creating a pediatric clinical genomics centre
To date, nine children from four different families have been identified as carriers of the mutation: three infants from Quebec, three from a Bengali family living in Toronto, and three Israelis, whose symptoms are less severe.
Dr. Michaud’s team discovered the genetic mutation by comparing the complete DNA of the Quebec family’s children with symptoms of the disease. The researchers then identified children, among other families, who carried the single candidate gene. The gene was revealed only in the affected children, but not in the unaffected children of the families studied.
The discovery comes at a time when CHU Sainte-Justine Mother and Child University Hospital has reached an agreement with Génome Québec to create the first pediatric clinical genomic centre in Canada. “This initiative will transform the quality of care for younger patients to ensure better prevention from childhood,” says Dr. Michaud. “More than 80% of genetic diseases occur in childhood or adolescence. “This new technology will allow us to sequence all the genes in the genome and obtain a genetic portrait of the children more quickly to know which disease they suffer from and to provide treatment, if available, or when it becomes available.”
(Source: nouvelles.umontreal.ca)
Study connects dots between genes and human behavior
Establishing links between genes, the brain and human behavior is a central issue in cognitive neuroscience research, but studying how genes influence cognitive abilities and behavior as the brain develops from childhood to adulthood has proven difficult.
Now, an international team of scientists has made inroads to understanding how genes influence brain structure and cognitive abilities and how neural circuits produce language.
The team studied individuals with a rare disorder known as Williams syndrome. By measuring neural activity in the brain associated with the distinct language skills and facial recognition abilities that are typical of the syndrome, they showed that Williams is due not to a single gene but to distinct subsets of genes, hinting that the syndrome is more complex than originally thought.
"Solutions to understanding the connections between genes, neural circuits and behavior are now emerging from a unique union of genetics and neuroscience," says Julie Korenberg, a University of Utah professor and an adjunct professor at the Salk Institute, who led the genetics aspects on the new study.
The study was led by Debra Mills, a professor of cognitive neuroscience at Bangor University in Wales. Ursula Bellugi, a professor at the Salk Institute for Biological Studies in La Jolla, was also integrally involved in the research.
Korenberg was convinced that with Mills’ approach of directly measuring the brain’s electrical firing they could solve the puzzle of precisely which genes were responsible for building the brain wiring underlying the different reaction to human faces in Williams syndrome.
"We also discovered," says Mills, "that in those with Williams syndrome, the brain processes language and faces abnormally from early childhood through middle age. This was a surprise because previous studies had suggested that part of the Williams brain functions normally in adulthood, with little understanding about how it developed."
The results of the study were published November 12, 2013 in Developmental Neuropsychology.
Williams syndrome is caused by the deletion of one of the two usual copies of approximately 25 genes from chromosome 7, resulting in mental impairment. Nearly everyone with the condition is missing these same genes, although a few rare individuals retain one or more genes that most people with Williams have lost. Korenberg was the early pioneer of studying these individuals with partial gene deletions as a way of gathering clues to the specific function of those genes and gene networks. The syndrome affects approximately 1 in 10,000 people around the world, including an estimated 20,000 to 30,000 individuals in the United States.
Although individuals with Williams experience developmental delays and learning disabilities, they are exceptionally sociable and possess remarkable verbal abilities and facial recognition skills in relation to their lower IQ. Bellugi has long observed that sociability also seems to drive language and has spent much of her career studying those with Williams syndrome.
"Williams offers us a window into how the brain works at many different levels," says Bellugi. "We have the tools to measure the different cognitive abilities associated with the syndrome, and thanks to Julie and Debbie we are now able to combine this with studies of the underlying genetic and neurological aspects."
Suspecting that specific genes might lie at the origins of brain plasticity, functional changes in the brain that occur with new knowledge or experiences, and that these genes might be linked to the unusual proficiencies of those with Williams, the team enrolled individuals of various ages in their study. They drew from children, adolescents and adults who all had the full genetic deletion for Williams syndrome and compared them with their non-affected peers. Their study is additionally significant for being one of the first to examine the brain structure and its functioning in children with Williams. And, as Korenberg predicted, a critical piece of the puzzle came from including in their study two adults with partial genetic deletions for Williams.
Using highly sensitive sensors to measure brain activity, the researchers, led by Mills, presented their study participants with both visual and auditory stimuli in the form of unfamiliar faces and spoken sentences. They charted the small changes in voltage generated by the areas of the brain responding to these stimuli, a process known as event-related potentials (ERPs). Mills was the first to publish studies on Williams syndrome using ERPs, developed the ERP markers for this study, and oversaw its design and analysis.
Mills identified ERP markers of brain plasticity in Williams syndrome in children and adults of varying ages and developmental stages. These findings are important because the brains of people with Williams are structured differently than those of people without the syndrome. In the Williams brain, the dorsal areas (along the back and top), which help control vision and spatial understanding, are undersized. The ventral areas (at the front and the bottom), which influence language, facial recognition, emotion and social drive, are relatively normal in size.
It was previously believed that in individuals with Williams, the ventral portion of the brain operated normally. What the team discovered, however, was that this area of the brain also processed information differently than those without the syndrome, and did so throughout development, from childhood to the adult years. This suggests that the brain was compensating in order to analyze information; in other words, it was exhibiting plasticity. Of additional importance, the distinct ERP markers identified by Mills are so characteristic of the different brain organization in Williams that this information alone is approximately 90 percent accurate when analyzing brain activity to identify someone with Williams syndrome.
Other key findings of the study resulted from comparing the ERPs of participants with full Williams deletion with those with partial genetic deletions. While psychological tests focused on facial recognition show no difference between these groups, the scientists found differences in these recognition abilities on the ERP measurements, which look directly at neural activity. Thus, the scientists were able to see how very slight genetic differences affected brain activity, which will allow them identify the roles of sub-sets of Williams genes in brain development and in adult facial recognition abilities.
By combining these one-in-a-million people with tools capable of directly measuring brain activity, the scientists now have the unprecedented opportunity to study the genetic underpinnings of mental disorders. The results of this study not only advance science’s understanding of the links between genes, the brain and behavior, but may lead to new insight into such disorders as autism, Down syndrome and schizophrenia.
"By greatly narrowing the specific genes involved in social disorders, our findings will help uncover targets for treatment and provide measures by which these and other treatments are successful in alleviating the desperation of autism, anxiety and other disorders," says Korenberg.
(Source: salk.edu)
Brain imaging differences in infants at genetic risk for Alzheimer’s
Researchers from Brown University and Banner Alzheimer’s Institute have found that infants who carry a gene associated with increased risk for Alzheimer’s disease tend to have differences in brain development compared to children without the gene. The study, published in JAMA Neurology, demonstrates some of the earliest developmental differences associated with a gene variant called APOE ε4, a common genotype and a known risk factor for late-onset Alzheimer’s.
The researchers imaged the brains of 162 healthy infants between the ages of two months and 25 months. All of the infants had DNA tests to see which variant of the APOE gene they carried. Sixty of them had the ε4 variant that has been linked to an increased risk of Alzheimer’s. Using a specialized MRI technique, the researchers compared the brains of ε4 carriers with non-carriers. They found that children who carry the APOE ε4 gene tended to have increased brain growth in areas in the frontal lobe, and decreased growth in areas in several areas in the middle and rear of the brain. The decreased growth was found in areas that tend to be affected in elderly patients who have Alzheimer’s disease.
Researchers emphasized that the findings do not mean that any of the children in the study are destined to develop Alzheimer’s or that the brain changes detected are the first clinical signs of the disease. What the findings do suggest, however, is that brains of APOE ε4 carriers tend to develop differently from those of non-ε4 carriers beginning very early in life. It is possible that these early changes provide a “foothold” for the later pathologies that lead to Alzheimer’s symptoms, the researchers say. Information from this study may be an important step toward understanding how this gene confers risk for Alzheimer’s, something that is not currently well understood.
“This work is about understanding how this gene influences brain development,” said Sean Deoni, who oversees Brown University’s Advanced Baby Imaging Lab and was one of the study’s senior authors. “These results do not establish a direct link to the changes seen in Alzheimer’s patients, but with more research they may tell us something about how the gene contributes to Alzheimer’s risk later in life.”
The APOE ε4 variant linked to Alzheimer’s is present in about 25 percent of the U.S. population. Not everyone who carries the gene gets Alzheimer’s, but 60 percent of people who develop the disease have at least one copy of the ε4 gene.
The gene is thought to have several different roles in the blood and brain, some of which remain to be clarified. For instance, it has been shown to participate in regulation of cholesterol, a molecule that is involved in the development of gray matter and white matter brain cells. It has also been shown to participate in the regulation of amyloid, a brain protein that accumulates in Alzheimer’s and is now being targeted by investigational treatments. Studies are needed to clarify the ways in which APOE, human development, aging and other risk factors may conspire to produce the brain changes involved in Alzheimer’s disease.
The researchers used an MRI technique developed at Brown’s Advanced Baby Imaging Lab. The technique quiets the MRI machine to a whisper, enabling the brains of healthy babies to be imaged while they sleep without medication. The technique also enables imaging of both gray matter — the part of the brain that contains neurons and nerve fibers — and white matter, which contains the fatty material that insulates the nerve fibers. Both gray and white matter are thought to have a role in Alzheimer’s. White matter growth begins shortly after birth and is an important measure of brain development.
“We’re in a good spot to be able to investigate how this gene influences development in healthy infants,” said Deoni, assistant professor of engineering at Brown. “These infants are not medicated and not showing any cognitive decline — quite the opposite, actually; they’re developing normally.”
There is no reason to believe that the children won’t continue to develop normally, Deoni said. There is no consistent evidence to suggest that ε4 carriers suffer any cognitive problems or developmental delay. And the areas of increased growth raise the possibility that the gene might actually confer some advantages to infants early on. Utimately the researchers hope the findings could lead to new strategies for preventing a disease that currently affects more than 5.2 million people in the U.S. alone.
“It may sound scary that we could detect these brain differences in infants,” said Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute in Arizona and another senior author on the paper. “But it is our sincere hope that an understanding of the earliest brain changes involved in the predisposition to Alzheimer’s will help researchers find treatments to prevent the clinical onset of Alzheimer’s disease — and do so long before these children become senior citizens.”
A critical theory in brain development
Experiments performed in the 1960s showed that rearing young animals with one eye closed dramatically altered brain development such that the parts of the visual cortex that would normally process information from the closed eye instead process information from the open eye. These effects can be induced only within a specific period of time—a ‘critical’ period during which the developing nervous system is particularly sensitive to its environment.
Subsequent work has shown that the onset of the critical period in the primary visual cortex requires the maturation of circuits containing neurons that synthesize and release an inhibitory neurotransmitter called gamma-aminobutyric acid (GABA). Now, Taro Toyoizumi and colleagues from the RIKEN Brain Science Institute have presented a theory that explains how this inhibition triggers the critical period.
The theory is based on a computer model of the primary visual cortex containing neurons that receive and process information from the eyes. The model incorporates spontaneous and visually evoked neuronal activity as reported in earlier studies. The simulation also incorporates an activity-dependent form of synaptic plasticity—the process by which connections between neurons are strengthened or weakened in response to neuronal activity.
During early development, spontaneous activity accounts for the majority of activity in the primary visual cortex. With time, however, spontaneous neuronal activity decreases whereas activity evoked by visual experiences increases. The new theory states that the critical period is triggered by the maturation of inhibitory neuronal circuitry, which suppresses the spontaneous activity in the primary visual cortex relative to the activity driven by incoming visual information.
The researchers turned to mice to find evidence to support the theory. Using electrodes to record primary visual cortex activity in freely moving mice, they showed as predicted by theory that the anti-anxiety drug diazepam, which enhances inhibitory activity, lowered the ratio of spontaneous to visual activity in mutant mice with weak inhibition—those lacking the gene encoding glutamic acid decarboxylase-65, an enzyme for synthesizing GABA. Such mice are known not to enter the critical period even in adulthood, but can be induced to do so by administration of diazepam.
Importantly, the theory explains distinct experience-dependent plasticity that takes place before the onset of the critical period, which has been observed in experiments but not explained by other theories. “In the future,” says Toyoizumi, “it would be useful to be able to control developmental plasticity stages by manipulating spontaneous activity in specific brain areas, which could have therapeutic applications.”
Pregnant mother’s stress affects baby’s gut and brain
Pregnant women may pass on the effects of stress to their fetus by way of bacterial changes in their vagina, suggests a study in mice. It may affect how well their baby’s brain is equipped to deal with stress in adulthood.
The bacteria in our body outnumber our own cells by about 10 to 1, with most of them found in our gut. Over the last few years, it has become clear that the bacterial ecosystem in our body – our microbiome – is essential for developing and maintaining a healthy immune system.
Our gut bugs also help to prevent germs from invading our bodies, and help to absorb nutrients from food.
A baby gets its first major dose of bacteria in life as it passes through its mother’s birth canal. En route, the baby ingests the mother’s vaginal microbes, which begin to colonise the newborn’s gut.
Chris Howerton, then at the University of Pennsylvania in Philadelphia, and his colleagues wanted to know if this initial population of bacteria is important in shaping a baby’s neurological development, and whether that population is influenced by stress during pregnancy.
Stressful pregnancy
The first step was to figure out what features of the mother’s vaginal microbiome might be altered by stress, and then see if any of those changes were transmitted to the offspring’s gut.
To do this, the team exposed 10 pregnant mice to a different psychologically stressful experience, such as exposing them to fox odour, keeping their cages lit at night, or temporarily restraining them every day for what would be the equivalent of the first trimester of their pregnancy. Another 10 pregnant mice were housed normally during the same time.
The team took samples of their vaginal bacteria throughout the pregnancy and again just after the mice had given birth. These samples were genetically sequenced to see what types of bacteria were present.
The microbiomes of the stressed mice were remarkably different to those of the unstressed mice after they had each given birth. There were more types of bacteria present, and the proportion of one common gut bacteria, Lactobacillus, was significantly reduced.
Like mother, like pup
To see whether these changes had been passed on to the pups, a few days after birth the pups’ nascent gut bacteria was removed from their colon and sequenced. Sure enough, the same bacterial patterns were seen in the pups of stressed mothers.
By analysing tissue from the pups’ hypothalamus – a brain area involved in hormone control, behaviour and sleep, among other things – the team was able to infer which genes were affected by the stress-induced changes in each mother’s microbiome.
They found that the expression of 20 genes was affected by the decrease in Lactobacillus, including genes related to the production of new neurons and the growth of synaptic connections in the brain.
These genetic outcomes in the brain are probably a result of a different suite of nutrients and metabolites circulating in the “stressed” pup’s blood, thanks to the altered gut flora they inherited. Indeed, when the team analysed the blood of the pups of the stressed mothers, they found that there were fewer molecules present necessary for the formation of essential neurotransmitters – chemicals that transmit signals to the brain. Furthermore, there were lower levels of a molecule thought to protect the brain from harmful oxidative stress.
"These changes are significant and are likely to be important for determining how the brain initially develops and how it will respond in the future to things like stress or changes in the environment," says Tracy Bale, Howerton’s supervisor during the research and director of the University of Pennsylvania lab.
As well as changing the nutrients available, the microbiome could also affect the brain via the immune system or by innervating the nerves in the gut that connect to it. “These three mechanisms aren’t mutually exclusive. It’s likely that they all play a role,” says Howerton.
Human angle
If the same effects are seen in humans, there may be a straightforward solution. “We can easily manipulate the bacteria we have inside of us,” says Howerton. For example, if a certain cocktail of bacteria is found to be beneficial to the newborns of stressed mothers, we could give it to them right after birth, he suggests. This approach could also benefit babies born via C-section, who do not pass through their mother’s birth canal, or those born to mothers whose gut bacteria has been disrupted as a result of antibiotic use during pregnancy.
Bale is now investigating the link between bacteria and brain development in pregnant women who have been through several traumatic experiences to analyse the effects on their babies’ gut bacteria. She also intends to follow their children’s behaviour as they grow up.
Resource rationale
"This is a remarkable trans-disciplinary study in how it bridged multiple organ systems to illuminate a complex question," says Catherine Hagan from the University of Missouri in Columbia. She says that more work needs to be done to show a causal link. "Mice are not tiny people – people are not big mice – more data is needed to understand how stress in mothers affects brain development in children," she says. "That said, mice and people have enough in common that this study provides a rationale for allocating resources to address such a concern."
"At the end of the day, most of what makes you ‘you’, and what drives your quality of life, comes down to the brain," says Bale. "It’s this very important, vulnerable tissue that is susceptible to many perturbations. If the microbiome is proven to be one of these driving forces, then it’s essential we know just how factors in our environment can change it and can reprogram the brain."
(Source: newscientist.com)
Exercise during pregnancy gives newborn brain development a head start
As little as 20 minutes of moderate exercise three times per week during pregnancy enhances the newborn child’s brain development, according to researchers at the University of Montreal and its affiliated CHU Sainte-Justine children’s hospital. This head-start could have an impact on the child’s entire life. “Our research indicates that exercise during pregnancy enhances the newborn child’s brain development,” explained Professor Dave Ellemberg, who led the study. “While animal studies have shown similar results, this is the first randomized controlled trial in humans to objectively measure the impact of exercise during pregnancy directly on the newborn’s brain. We hope these results will guide public health interventions and research on brain plasticity. Most of all, we are optimistic that this will encourage women to change their health habits, given that the simple act of exercising during pregnancy could make a difference for their child’s future.” Ellemberg and his colleagues Professor Daniel Curnier and PhD candidate Élise Labonté-LeMoyne presented their findings today at the Neuroscience 2013 congress in San Diego.
Not so long ago, obstetricians would tell women to take it easy and rest during their pregnancy. Recently, the tides have turned and it is now commonly accepted that inactivity is actually a health concern. “While being sedentary increases the risks of suffering complications during pregnancy, being active can ease post-partum recovery, make pregnancy more comfortable and reduce the risk of obesity in the children,” Curier explained. “Given that exercise has been demonstrated to be beneficial for the adult’s brain, we hypothesized that it could also be beneficial for the unborn child through the mother’s actions.”
To verify this, starting at the beginning of their second trimester, women were randomly assigned to an exercise group or a sedentary group. Women in the exercise group had to perform at least 20 minutes of cardiovascular exercise three times per week at a moderate intensity, which should lead to at least a slight shortness of breath. Women in the sedentary group did not exercise. The brain activity of the newborns was assessed between the ages of 8 to 12 days, by means of electroencephalography, which enables the recording of the electrical activity of the brain. “We used 124 soft electrodes placed on the infant’s head and waited for the child to fall asleep on his or her mother’s lap. We then measured auditory memory by means of the brain’s unconscious response to repeated and novel sounds,” Labonté-LeMoyne said. “Our results show that the babies born from the mothers who were physically active have a more mature cerebral activation, suggesting that their brains developed more rapidly.”
The researchers are now in the process of evaluating the children’s cognitive, motor and language development at age 1 to verify if these differences are maintained.
(Source: nouvelles.umontreal.ca)
Researchers identify molecule that orients neurons for high definition sensing
Many animals have highly developed senses, such as vision in carnivores, touch in mice, and hearing in bats. New research from the RIKEN Brain Science Institute has uncovered a brain molecule that can explain the existence of such finely-tuned sensory capabilities, revealing how brain cells responsible for specific senses are positioned to receive incoming sensory information.
The study, led by Dr. Tomomi Shimogori and published in the journal Science, sought to uncover the molecule that enables high acuity sensing by examining brain regions that receive information from the senses. They found that areas responsible for touch in mice and vision in ferrets contain a protein called BTBD3 that optimizes neuronal shape to receive sensory input more efficiently.
Neurons have a highly specialized shape, sending signals through one long projection called an axon, while receiving signals from many branch-like projections called dendrites. The final shape and connections to other neurons are typically completed after birth. Some neurons have dendrites distributed equally all around the cell body, like a starfish, while in others they extend only from one side, like a squid, steering towards axons that are actively bringing in information from the peripheral nerves. It was previously unknown what enables neurons to have highly oriented dendrites.
“We were fascinated by the dendrite patterning changes that occurred during the early postnatal stage that is controlled by neuronal input,” says Dr. Shimogori. “We found a fundamental process that is important to remove unnecessary dendrites to prevent mis-wiring and to make efficient neuronal circuits.”
The researchers searched for genes that are active exclusively in the mouse somatosensory cortex, the brain region responsible for their sense of touch, and found that the gene coding for the protein BTBD3 was active in the neurons of the barrel cortex, which receives input from their whiskers, the highly sensitive tactile sensors in mice, and that these neurons had unidirectional dendrites.
Using gene manipulations in embryonic mouse brain the authors found that eliminating BTBD3 made dendrites uniformly distribute around neurons in the mouse barrel cortex. In contrast, artificially introducing BTBD3 in the visual cortex of mice where BTBD3 is not normally found, reoriented the normally symmetrically positioned dendrites to one side. The same mechanism shaped neurons in the visual cortex of ferrets, which unlike the mouse contains BTBD3.
“High acuity sensory function may have been enabled by the evolution of BTBD3 and related proteins in brain development,” adds Dr. Shimogori. “Finding BTBD3 selectively in the visual and auditory cortex of the common marmoset, a species that relies heavily on high acuity vocal and visual communication for survival, and in mouse, where it is expressed in high-acuity tactile and olfactory areas, but not in low acuity visual cortex, supports this idea.” The authors plan to examine their theory by testing sensory function in mice without BTBD3 gene expression.
(Source: riken.jp)
Exposure to Cortisol-Like Medications Before Birth May Contribute to Emotional Problems and Brain Changes
Neonatologists seem to perform miracles in the fight to support the survival of babies born prematurely.
To promote their survival, cortisol-like drugs called glucocorticoids are administered frequently to women in preterm labor to accelerate their babies’ lung maturation prior to birth. Cortisol is a substance naturally released by the body when stressed. But the levels of glucocorticoids administered to promote lung development are higher than that achieved with typical stress, perhaps only mirrored in the body’s reaction to extreme stresses.
The benefit of glucocorticoids is undisputed and has certainly saved the lives of countless babies, but this exposure also may have some negative consequences. Indeed, excessive glucocorticoid levels may have effects on brain development, perhaps contributing to emotional problems later in life.
In this issue of Biological Psychiatry, Dr. Elysia Davis at the University of Denver and her colleagues report new findings on the effects of synthetic glucocorticoid on human brain development. Their study focused on healthy children who were born full-term, avoiding the confounding effects of premature birth.
The investigators conducted brain imaging sessions in and carefully assessed 54 children, 6-10 years of age. The mothers of the participating children also completed reports on their child’s behavior. The researchers then divided the children into two groups: those who were exposed to glucocorticoids prenatally and those who were not.
In this study, children with fetal glucocorticoid exposure showed significant cortical thinning, and a thinner cortex also predicted more emotional problems. In one particularly affected part of the brain, the rostral anterior cingulate cortex, it was 8-9% thinner among children exposed to glucocorticoids. Interestingly, other studies have shown that this region of the brain is affected in individuals diagnosed with mood and anxiety disorders.
"Fetal exposure to a frequently administered stress hormone is associated with consequences for child brain development that persist for at least 6 to 10 years. These neurological changes are associated with increased risk for stress and emotional problems," Davis explained of their findings. "Importantly, these findings were observed among healthy children born full term."
Although such a finding does not indicate that glucocorticoids ‘caused’ these changes, the researchers did determine that the findings can’t be explained by any obvious confounding differences between the groups. The two groups did not differ on weight or gestational age at birth, apgar scores, maternal factors, or any other basic demographics. Thus, the findings do suggest that glucocorticoid administration may somehow alter the trajectory of brain development of exposed children.
"This study provides evidence that prenatal exposure to stress hormones shapes the construction of the fetal nervous system with consequences for the developing brain that persist into the preadolescent period," she added.
"This study highlights potential links between early cortisol exposure, cortical thinning and mood symptoms in children. It may provide important insights into the development of the brain and the long-term impact of maternal stress," commented Dr. John Krystal, Editor of Biological Psychiatry.
(Source: elsevier.com)
Nurturing may protect kids from brain changes linked to poverty
Growing up in poverty can have long-lasting, negative consequences for a child. But for poor children raised by parents who lack nurturing skills, the effects may be particularly worrisome, according to a new study at Washington University School of Medicine in St. Louis.
Among children living in poverty, the researchers identified changes in the brain that can lead to lifelong problems like depression, learning difficulties and limitations in the ability to cope with stress. The study showed that the extent of those changes was influenced strongly by whether parents were nurturing.
The good news, according to the researchers, is that a nurturing home life may offset some of the negative changes in brain anatomy among poor children. And the findings suggest that teaching nurturing skills to parents — particularly those living in poverty — may provide a lifetime benefit for their children.
The study is published online Oct. 28 and will appear in the November issue of JAMA Pediatrics.
Using magnetic resonance imaging (MRI), the researchers found that poor children with parents who were not very nurturing were likely to have less gray and white matter in the brain. Gray matter is closely linked to intelligence, while white matter often is linked to the brain’s ability to transmit signals between various cells and structures.
The MRI scans also revealed that two key brain structures were smaller in children who were living in poverty: the amygdala, a key structure in emotional health, and the hippocampus, an area of the brain that is critical to learning and memory.
“We’ve known for many years from behavioral studies that exposure to poverty is one of the most powerful predictors of poor developmental outcomes for children,” said principal investigator Joan L. Luby, MD, a Washington University child psychiatrist at St. Louis Children’s Hospital. “A growing number of neuroscience and brain-imaging studies recently have shown that poverty also has a negative effect on brain development.
“What’s new is that our research shows the effects of poverty on the developing brain, particularly in the hippocampus, are strongly influenced by parenting and life stresses that the children experience.”
Luby, a professor of psychiatry and director of the university’s Early Emotional Development Program, is in the midst of a long-term study of childhood depression. As part of the Preschool Depression Study, she has been following 305 healthy and depressed kids since they were in preschool. As the children have grown, they also have received MRI scans that track brain development.
“We actually stumbled upon this finding,” she said. “Initially, we thought we would have to control for the effects of poverty, but as we attempted to control for it, we realized that poverty was really driving some of the outcomes of interest, and that caused us to change our focus to poverty, which was not the initial aim of this study.”
In the new study, Luby’s team looked at scans from 145 children enrolled in the depression study. Some were depressed, others healthy, and others had been diagnosed with different psychiatric disorders such as ADHD (attention-deficit hyperactivity disorder). As she studied these children, Luby said it became clear that poverty and stressful life events, which often go hand in hand, were affecting brain development.
The researchers measured poverty using what’s called an income-to-needs ratio, which takes a family’s size and annual income into account. The current federal poverty level is $23,550 for a family of four.
Although the investigators found that poverty had a powerful impact on gray matter, white matter, hippocampal and amygdala volumes, they found that the main driver of changes among poor children in the volume of the hippocampus was not lack of money but the extent to which poor parents nurture their children. The hippocampus is a key brain region of interest in studying the risk for impairments.
Luby’s team rated nurturing using observations made by the researchers — who were unaware of characteristics such as income level or whether a child had a psychiatric diagnosis — when the children came to the clinic for an appointment. And on one of the clinic visits, the researchers rated parental nurturing using a test of the child’s impatience and of a parent’s patience with that child.
While waiting to see a health professional, a child was given a gift-wrapped package, and that child’s parent or caregiver was given paperwork to fill out. The child, meanwhile, was told that s/he could not open the package until the caregiver completed the paperwork, a task that researchers estimated would take about 10 minutes.
Luby’s team found that parents living in poverty appeared more stressed and less able to nurture their children during that exercise. In cases where poor parents were rated as good nurturers, the children were less likely to exhibit the same anatomical changes in the brain as poor children with less nurturing parents.
“Parents can be less emotionally responsive for a whole host of reasons,” Luby said. “They may work two jobs or regularly find themselves trying to scrounge together money for food. Perhaps they live in an unsafe environment. They may be facing many stresses, and some don’t have the capacity to invest in supportive parenting as much as parents who don’t have to live in the midst of those adverse circumstances.”
The researchers also found that poorer children were more likely to experience stressful life events, which can influence brain development. Anything from moving to a new house to changing schools to having parents who fight regularly to the death of a loved one is considered a stressful life event.
Luby believes this study could provide policymakers with at least a partial answer to the question of what it is about poverty that can be so detrimental to a child’s long-term developmental outcome. Because it appears that a nurturing parent or caregiver may prevent some of the changes in brain anatomy that this study identified, Luby said it is vital that society invest in public health prevention programs that target parental nurturing skills. She suggested that a key next step would be to determine if there are sensitive developmental periods when interventions with parents might have the most powerful impact.
“Children who experience positive caregiver support don’t necessarily experience the developmental, cognitive and emotional problems that can affect children who don’t receive as much nurturing, and that is tremendously important,” Luby said. “This study gives us a feasible, tangible target with the suggestion that early interventions that focus on parenting may provide a tremendous payoff.”