Brain Scans Show The Real Impact Love Has On A Child’s Brain.


You comfort them over a skinned knee in the playground, and coax them to sleep with a soothing lullaby. But being a nurturing mother is not just about emotional care – it pays dividends by determining the size of your child’s brain, scientists say.

Both of these images are brain scans of a two three-year-old children, but the brain on the left is considerably larger, has fewer spots and less dark areas, compared to the one on the right.

According to neurologists this sizable difference has one primary cause – the way each child was treated by their mothers.

But the child with the shrunken brain was the victim of severe neglect and abuse.

Babies’ brains grow and develop as they interact with their environment and learn how to function within it.

When babies’ cries bring food or comfort, they are strengthening the neuronal pathways that help them learn how to get their needs met, both physically and emotionally. But babies who do not get responses to their cries, and babies whose cries are met with abuse, learn different lessons.

The neuronal pathways that are developed and strengthened under negative conditions prepare children to cope in that negative environment, and their ability to respond to nurturing and kindness may be impaired.

According to research reported by the newspaper, the brain on the right in the image above worryingly lacks some of the most fundamental areas present in the image on the left.

The consequences of these deficits are pronounced – the child on the left with the larger brain will be more intelligent and more likely to develop the social ability to empathise with others.

This type of severe, global neglect can have devastating consequences. The extreme lack of stimulation may result in fewer neuronal pathways available for learning.

The lack of opportunity to form an attachment with a nurturing caregiver during infancy may mean that some of these children will always have difficulties forming meaningful relationships with others. But studies have also found that time played a factor–children who were adopted as young infants have shown more recovery than children who were adopted as toddlers.

But in contrast, the child with the shrunken brain will be more likely to become addicted to drugs and involved in violent crimes, much more likely to be unemployed and to be dependent on state benefits.
The child is also more likely to develop mental and other serious health problems.

Some of the specific long-term effects of abuse and neglect on the developing brain can include:

  • Diminished growth in the left hemisphere, which may increase the risk for depression
  • Irritability in the limbic system, setting the stage for the emergence of panic disorder and posttraumatic stress disorder
  • Smaller growth in the hippocampus and limbic abnormalities, which can increase the risk for dissociative disorders and memory impairments
  • Impairment in the connection between the two brain hemispheres, which has been linked to symptoms of attention-deficit/hyperactivity disorder

Professor Allan Schore, of UCLA, told The Sunday Telegraph that if a baby is not treated properly in the first two years of life, it can have a fundamental impact on development.

He pointed out that the genes for several aspects of brain function, including intelligence, cannot function.
And sadly there is a chance they may never develop and come into existence.

These has concerning implications for neglected children that are taken into care past the age of two.
It also seems that the more severe the mother’s neglect, the more pronounced the damage can be.

The images also have worrying consequences for the childhood neglect cycle – often parents who, because their parents neglected them, do not have fully developed brains, neglect their own children in a similar way.

But research in the U.S. has shown the cycle can be successfully broken if early intervention is staged and families are supported.

The study correlates with research released earlier this year that found that children who are given love and affection from their mothers early in life are smarter with a better ability to learn.

The experiences of infancy and early childhood provide the organizing framework for the expression of children’s intelligence, emotions, and personalities.

When those experiences are primarily negative, children may develop emotional, behavioral, and learning problems that persist throughout their lifetime, especially in the absence of targeted interventions.

The study by child psychiatrists and neuroscientists at Washington University School of Medicine in St. Louis, found school-aged children whose mothers nurtured them early in life have brains with a larger hippocampus, a key structure important to learning, memory and response to stress.

The research was the first to show that changes in this critical region of children’s brain anatomy are linked to a mother’s nurturing, Neurosciencenews.com reports.

The research is published online in the Proceedings of the National Academy of Sciences Early Edition.
Lead author Joan L. Luby, MD, professor of child psychiatry, said the study reinforces how important nurturing parents are to a child’s development.

Sources:
childwelfare.gov

preventdisease.com

         

Scientists identify clue to regrowing nerve cells.


Researchers atWashington University School of Medicine in St. Louis have identified a chain reaction that triggers the regrowth of some damaged nerve cell branches, a discovery that one day may help improve treatments for nerve injuries that can cause loss of sensation or paralysis. 

The scientists also showed that nerve cells in the brain and spinal cord are missing a link in this chain reaction. The link, a protein called HDAC5, may help explain why these cells are unlikely to regrow lost branches on their own. The new research suggests that activating HDAC5 in the central nervous system may turn on regeneration of nerve cell branches in this region, where injuries often cause lasting paralysis. 

Nerve cells with branches

“We knew several genes that contribute to the regrowth of these nerve cell branches, which are called axons, but until now we didn’t know what activated the expression of these genes and, hence, the repair process,” said senior author Valeria Cavalli, PhD, assistant professor of neurobiology. “This puts us a step closer to one day being able to develop treatments that enhance axon regrowth.” 

The research appears Nov. 7 in the journal Cell.

Axons are the branches of nerve cells that send messages. They typically are much longer and more vulnerable to injury than dendrites, the branches that receive messages. 

In the peripheral nervous system — the network of nerve cells outside the brain and spinal column — cells sometimes naturally regenerate damaged axons. But in the central nervous system, comprised of the brain and spinal cord, injured nerve cells typically do not replace lost axons. 

Working with peripheral nervous system cells grown in the laboratory, Yongcheol Cho, PhD, a postdoctoral research associate in Cavalli’s laboratory, severed the cells’ axons. He and his colleagues learned that this causes a surge of calcium to travel backward along the axon to the body of the cell. The surge is the first step in a series of reactions that activate axon repair mechanisms. 

In peripheral nerve cells, one of the most important steps in this chain reaction is the release of a protein, HDAC5, from the cell nucleus, the central compartment where DNA is kept. The researchers learned that after leaving the nucleus, HDAC5 turns on a number of genes involved in the regrowth process. HDAC5 also travels to the site of the injury to assist in the creation of microtubules, rigid tubes that act as support structures for the cell and help establish the structure of the replacement axon.

When the researchers genetically modified the HDAC5 gene to keep its protein trapped in the nuclei of peripheral nerve cells, axons did not regenerate in cell cultures. The scientists also showed they could encourage axon regrowth in cell cultures and in animals by dosing the cells with drugs that made it easier for HDAC5 to leave the nucleus.

When the scientists looked for the same chain reaction in central nervous system cells, they found that HDAC5 never left the nuclei of the cells and did not travel to the site of the injury. They believe that failure to get this essential player out of the nucleus may be one of the most important reasons why central nervous system cells do not regenerate axons.

“This gives us the hope that if we can find ways to manipulate this system in brain and spinal cord neurons, we can help the cells of the central nervous system regrow lost branches,” Cavalli said. “We’re working on that now.”

Cavalli also is collaborating with Susan Mackinnon, MD, the Sydney M. Shoenberg Jr. and Robert H. Shoenberg Professor of Surgery, chief of the Division of Plastic and Reconstructive Surgery and a pioneer in peripheral nerve transplants. The two are investigating whether HDAC5 or other components of the chain reaction can be used to help restore sensory functions in nerve grafts.

 

Childhood Poverty Linked to Poor Brain Development.


Exposure to poverty in early childhood negatively affects brain development, but good-quality caregiving may help offset this effect, new research suggests.

A longitudinal imaging study shows that young children exposed to poverty have smaller white and cortical gray matter as well as hippocampal and amygdala volumes, as measured during school age and early adolescence.

“These findings extend the substantial body of behavioral data demonstrating the deleterious effects of poverty on child developmental outcomes into the neurodevelopmental domain and are consistent with prior results,” the investigators, with lead author Joan Luby, MD, Washington University School of Medicine in St. Louis, Missouri, write.

However, the investigators also found that the effects of poverty on hippocampal volume were influenced by caregiving and stressful life events.

The study was published online October 28 in JAMA Pediatrics.

Powerful Risk Factor

Poverty is one of the most powerful risk factors for poor developmental outcomes; a large body of research shows that children exposed to poverty have poorer cognitive outcomes and school performance and are at greater risk for antisocial behaviors and mental disorders.

However, the researchers note, there are few neurobiological data in humans to inform the mechanism of these relationships.

“This represents a critical gap in the literature and an urgent national and global public health problem based on statistics that more than 1 in 5 children are now living below the poverty line in the United States alone,” the authors write.

To examine the effects of poverty on childhood brain development and to understand what factors might mediate its negative impact, the researchers used magnetic resonance imaging (MRI) to examine total white and cortical gray matter as well as hippocampal and amygdala volumes in 145 children aged 6 to 12 years who had been followed since preschool.

The researchers looked at caregiver support/hostility, measured observationally during the preschool period, and stressful life events, measured prospectively.

The children underwent annual behavioral assessments for 3 to 6 years prior to MRI scanning and were annually assessed for 5 to 10 years following brain imaging.

Household poverty was measured using the federal income-to-needs ratio.

“Toxic” Effect

The researchers found that poverty was associated with lower hippocampal volumes, but they also found that caregiving behaviors and stressful life events could fully mediate this negative effect.

“The finding that the effects of poverty on hippocampal development are mediated through caregiving and stressful life events further underscores the importance of high-quality early childhood caregiving, a task that can be achieved through parenting education and support, as well as through preschool programs that provide high-quality supplementary caregiving and safe haven to vulnerable young children,” the investigators write.

In an accompanying editorial, Charles A. Nelson, PhD, Boston Children’s Hospital and Harvard Medical School, in Massachusetts, notes that the findings show that early experience “weaves its way into the neural and biological infrastructure of the child in such a way as to impact development trajectories and outcomes.”

“Exposure to early life adversity should be considered no less toxic than exposure to lead, alcohol or cocaine, and, as such it merits similar attention from health authorities,” Dr. Nelson writes.

New Tools Enhance Molecular Portraits of Breast Cancers.


Using a combination of analytical tools, investigators with The Cancer Genome Atlas (TCGA) Research Network have completed a molecular study of breast tumors from 825 women. The results, recently reported in Nature, confirm the existence of four major subtypes of breast cancer and add new details about the biological changes underlying these diseases.

The researchers used up to six different technologies to characterize subsets of the tumors. In addition to sequencing DNA and RNA, the investigators profiled patterns of DNA methylation and counted the number of copies of genes in tumors. This was also the first TCGA study to report protein expression patterns in tumor samples.

The integration of these results has given researchers a catalog of the genetic and epigenetic abnormalities in each subtype of breast cancer, underscoring the idea that these tumors are, in many respects, distinct diseases.

“This paper and five others [describing breast cancer genomes] published this year in Nature provide a new roadmap for translational and basic research on breast cancer,” said co-lead investigator Dr. Matthew Ellis of the Washington University School of Medicine in St. Louis. Researchers could spend a decade following up on these results, he added. (See the sidebar for links to the study abstracts.)

Previous studies had hinted that one of the subtypes, basal-like breast cancer, was genetically similar to a form of ovarian cancer. The TCGA study confirmed this idea and suggested that treatments currently being tested for some ovarian cancers could be tested against these breast cancers.

“This finding really stood out,” said Dr. Ellis. “And it led to discussions [among the study authors] about the most appropriate types of chemotherapy for patients with breast cancer.” The other subtypes are known as luminal A, luminal B, and HER2-enriched breast cancers.

Making Use of Multiple Technologies

Speaking at a press briefing on cancer research last week, NCI Director Dr. Harold Varmus acknowledged that the four breast cancer subtypes have been known for years. What’s new, he explained, is that, for each subtype, TCGA investigators used multiple technologies to describe the “landscape of genetic abnormalities” in greater detail than in the past.

The Six Nature Studies

“We haven’t had a storehouse of so much valuable information about each of these categories of cancer, with the same tumors analyzed for a wide variety of properties,” he said. “It’s the repository that is so important.”

Because the study included hundreds of tumors, the researchers were able to detect uncommon but recurring mutations. Some of these mutations indicated that the tumors might respond to existing drugs. “Repurposing drugs will be important for treating this disease,” said Dr. Ellis.

Even if a particular mutation occurs in only 2 percent of patients, Dr. Ellis continued, breast cancer is common enough that researchers should be able to enroll enough women in clinical trials to test existing drugs that target these mutations.

About 20 percent of the patients with basal-like tumors might be candidates for drugs known as PARP inhibitors based on analyses of the genes BRCA1 and BRCA2 in their tumors, the researchers said. The group of basal-like tumors includes triple-negative breast cancers, which are difficult to treat and disproportionately affect younger women and African Americans.

The Translation Phase

Only three genes—TP53, PIK3CA, and GATA3—were mutated in more than 10 percent of the patients’ tumors. Drugs that target changes resulting from defects in PIK3CA are in development and could be tested in selected patients with breast cancer. However, designing and implementing large clinical trials can take years, the researchers cautioned.

“People always want to know when this kind of research is going to affect clinical care,” said Dr. Charles Perou of the Lineberger Comprehensive Cancer Center at the University of North Carolina, another study leader. “Now that we’ve made these discoveries, we’re in the translation phase.”

Many of the new discoveries can now be tested in the context of clinical trials. For instance, the study suggested there may be at least two groups of patients with HER2-positive tumors, and these groups may have different responses to treatment.

“We had a hint of this from past gene-expression studies,” said Dr. Perou. But the integrated results of the TCGA analysis, which included proteomics, are “far more convincing and suggestive than results based on any one technology alone.”

Dr. Perou co-authored one of the first studies to use genomics to distinguish subtypes of cancer. The study, published in 2000, used what was then a new tool—DNA microarrays—to profile the expression of 8,000 genes in breast tumors from 42 women.

More than a decade later, the technological advances in genomics have been “astonishing,” noted Dr. Ellis. The missing component right now is information about proteins and the biochemistry of cancer cells, he observed.

“Over the next 10 years, we need to study proteins in the same way that we have just studied DNA and RNA over the last decade,” said Dr. Ellis. Only then, he added, “will we develop a complete picture of the biochemistry of cancer cells.”

Source: NCI

 

 

The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries.


CD133+ cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133+ cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133+ cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133+ cells to induce or enhance the repair of injured peripheral nerves.

Methods

Phosphate-buffered saline (PBS group [Group 1]), 105 fresh CD133+ cells (fresh group [Group 2]), 105 ex vivo expanded CD133+ cells (expansion group [Group 3]), or 104 fresh CD133+ cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed.

Results

After 1 week of expansion culture, the number of cells increased 9.6 ± 3.3–fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133+ cell population contained 93.22% ± 0.30% CD133+ cells and further confirmed that the expanded cells had a purity of 59.02% ± 1.58% CD133+ cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1.

Conclusions

The authors’ results show that ex vivo expanded CD133+ cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133+ cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133+ cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting.

Source: Journal of Neurosurgery.

 

Sequencing of Single Sperm Could Reveal New Infertility Causes.


Sperm, decoded: a technological achievement parses the genomes of individual sperm cells, showing a new way to study reproductive medicine and hereditary cancer

Less than a decade after the first full human genome was mapped, technology has arrived to decode the full genome of a single sex cell. The ability promises to offer new insight into the causes of infertility, the development of mutations and the diversity of the human genome.

Sperm and egg cells differ from other bodily cells in that they have a single—rather than double—set of chromosomes. Researchers have successfully amplified and sequenced 91 sperm cells from a single individual, a 40-year-old man whose genome has already been sequenced and analyzed—an important factor for checking the accuracy of the sperm sequencing. They found that the sampled sperm had sustained about 23 recombinations, which help to mix up genes from the chromosomes to increase genetic diversity in offspring, and between 25 and 36 new mutations, rates that match previous estimations for those in the general population. The scientists reported the findings online July 19 in Cell.

The new capability is “going to allow us to answer a lot of questions about genome stability in the germ line,” says Don Conrad, a human geneticist at Washington University School of Medicine in Saint Louis, who was not involved with the new research. The researchers found that although the man who donated the sperm already had healthy offspring, two of the sperm cells studied were each missing a full chromosome. Such mutations, however, make it less likely that a sperm cell will successfully fertilize an egg.

Until now, we have made rough estimates about genetic mutations and recombination on the population scale. “We haven’t had the tools to quantify those things on a personal level,” Conrad says. “This is a technological breakthrough.” Stephen Quake of the Stanford School of Medicine‘s Department of Bioengineering and his team have been working on this project for the past decade. “We started with bacteria and worked our way up to humans,” he says. They harnessed developments in the field of micro-fluidics to sequence the single cells on chips. These micro-fluidic chips allowed them to amplify the genome (with a process called multiple displacement amplification) using far less material, which reduced the odds for contamination—and thus erroneous findings—by 1,000 times, they reported.

The approach also revealed new places where mutations seem to congregate on the genome—so-called hot spots. Although the study was not designed to pinpoint particular biological signals, it demonstrates “how little we actually knew about hot spots across the genome,” Quake says. And future research can use these findings—and technology—to start to probe bigger biological questions, such as “to help understand and potentially diagnose reproductive disorders, to help understand what happens when it’s the man’s fault,” he says.

Reproductive technologists, however, will not be sequencing sperm to screen them for implantation anytime soon. The current method of sequencing destroys the sperm cell subject. Quake, however, suggests that both screening and capturing a sperm cell intact is possible under the right conditions—namely, just before a sperm cell splits through meiosis. “If you can capture them before they separate, you can sequence one and you’ll know what the other is.”

The ability to sequence these single sex cells will open a new window to study infertility. “I think there are forms of infertility out there waiting to be identified that don’t even have a name yet,” Conrad says. He estimates that the technology could be validated and ready for clinical use within five years. The next hurdle, he says, is not technological but biological: scientists do not yet know entirely what genetic changes might be linked to various fertility challenges—a major step before diagnostic tests can be developed and rolled out.

Some couples are already testing for inherited mutations that could cause disease before an embryo is implanted in the uterus. These existing genetic tests have also made clear that there are other considerations before genome screening for sperm could become widespread. One is a “complicated legal landscape,” Conrad points out. When clinicians do a full genome screen, they can find anything, such as a mutation that puts one at higher risk for a certain cancer. But it has not yet been established whether they are obligated to look for these mutations or tell patients if they find them. “Conceptually, it’s straightforward to do genome sequencing,” but layering on the clinical considerations and genetic counseling can make such screening thornier than it might first appear.

Sequencing a full genome from a single cell also holds promise for a variety of medical fields outside of reproduction. Quake and his team are already looking into cancer cells, which have “enormous genetic variation,” he says. Cancer cells, however, have two sets of chromosomes (as do most of the body’s cells), making them more difficult to genetically parse than sperm or egg cells, which have just one set of chromosomes.

Nevertheless, this technology could improve monitoring to look for specific genetic signatures of circulating cancer cells, he notes. “There’s quite a bit to do,” Quake says. But now that the technology is ready, “you can start thinking about those critical studies.”

Source: Scientific American.