Connect with us

News

Scoliosis Linked To Essential Mineral

Published

on

Nobody knows why some children’s backs start to curve to one side just as they hit puberty. Most children diagnosed with scoliosis, or curvature of the spine, have no known risk factors.

A new study suggests that the body’s inability to fully utilize the essential dietary mineral manganese might be to blame for some cases of severe scoliosis. Researchers at Washington University School of Medicine in St. Louis have found that children with severe scoliosis are twice as likely as children without the disease to carry a gene variant that makes it hard for their cells to take in and use manganese. Manganese is required for growing bones and cartilage.

“Our study links a common disease — scoliosis — to something that’s potentially modifiable in the diet,” said senior author Christina Gurnett, MD, PhD, a professor of neurology, of orthopedic surgery and of pediatrics.

“But we don’t want people to go out right now and start manganese supplements, because we already know that too much manganese can be harmful.”

The study is published Oct. 9 in Nature Communications.

About 3 million new cases of scoliosis are diagnosed every year. Most are mild and require only that doctors keep a watchful eye on the condition. Children who develop a moderate bend to their spine may need to wear a back brace until they finish growing. In rare cases, the curvature is so pronounced that it requires surgery to correct.

Cases of scoliosis tend to cluster in families, but not in a simple way, which suggests that many different genes each play a small role in increasing the risk of the disease. To identify such genes, Gurnett and a research team including Matthew Dobbs, MD, the Dr. Asa C and Mrs. Dorothy W. Jones Professor of Orthopaedic Surgery, and postdoctoral researcher and first author Gabriel Haller, PhD, scanned all the genes in 457 children with severe scoliosis and 987 children without scoliosis.

They found a variant in the gene SLC39A8 in only 6 percent of the healthy children but 12 percent of the children with severe scoliosis. A second analysis in a separate group of 1,095 healthy children and 841 children with moderate to severe scoliosis also found that children with scoliosis were about twice as likely to carry the variant.

When the researchers bred zebrafish with a disabled SLC39A8 gene, the fish developed movement and skeletal abnormalities, including curves in their spines.

This gene hasn’t been studied much, but there are some reports that it helps cells take in minerals such as zinc, iron and manganese. Haller and Gurnett found that human cells with the gene variant successfully took up zinc and iron but failed to take in manganese. They also discovered that children with the gene variant had significantly lower levels of manganese in their blood than those with the more common form — although both groups were still within the normal range.

“Our goal in studying the genetics of this disorder was to see if there was anything we could learn that might change how we treat patients,” said Gurnett, who is also director of the Division of Pediatric and Developmental Neurology and neurologist-in-chief at St. Louis Children’s Hospital.

“And we came across this gene variant that affects the level of manganese in the body. That tells me maybe we should start thinking about studying nutritional treatments for some children at risk.”

Manganese is both an essential mineral and a toxin. High doses can cause manganism, a permanent neurological condition characterized by tremors and difficulty walking, as well as psychiatric symptoms such as aggression and hallucinations. The mineral also has been linked to Parkinson’s disease, schizophrenia and high blood pressure. Too little manganese, on the other hand, can cause manganese deficiency — although this is rarely seen in people because the human body needs only trace amounts that are easily obtained from food. But animal studies show that lack of manganese can result in problems metabolizing fat and sugar, impaired growth, difficulty walking and curvature of the spine.

The children with the genetic variant did not have manganese deficiency, but they may be unable to use manganese as efficiently as others.

“The genetic variant does not stop the gene from working entirely, it’s just not working optimally,” Haller said.

“So maybe most people need a certain level of manganese in their blood, but if you have a bad gene variant like this one, you need more.”

Any manganese supplementation would have to be carefully measured to avoid raising the risk for other serious diseases, the researchers cautioned.

“We’ve started doing these studies in zebrafish by adding manganese to their water,” Gurnett said.

“But we still need to do human studies to figure out how much exactly is both safe and effective.”

News

Paternal Transmission Of Epigenetic Memory Via Sperm

Published

on

Studies of human populations and animal models suggest that a father’s experiences such as diet or environmental stress can influence the health and development of his descendants. How these effects are transmitted across generations, however, remains mysterious.

Susan Strome’s lab at UC Santa Cruz has been making steady progress in unraveling the mechanisms behind this phenomenon, using a tiny roundworm called Caenorhabditis elegans to show how marks on chromosomes that affect gene expression, called “epigenetic” marks, can be transmitted from parents to offspring. Her team’s most recent paper, published October 17 in Nature Communications, focuses on transmission of epigenetic marks by C. elegans sperm.

In addition to documenting the transmission of epigenetic memory by sperm, the new study shows that the epigenetic information delivered by sperm to the embryo is both necessary and sufficient to guide proper development of germ cells in the offspring (germ cells give rise to eggs and sperm).

“We decided to look at C. elegans because it is such a good model for asking epigenetic questions using powerful genetic approaches,” said Strome, a distinguished professor of molecular, cell, and developmental biology.

Epigenetic changes do not alter the DNA sequences of genes, but instead involve chemical modifications to either the DNA itself or the histone proteins with which DNA is packaged in the chromosomes. These modifications influence gene expression, turning genes on or off in different cells and at different stages of development. The idea that epigenetic modifications can cause changes in gene expression that are transmitted from one generation to the next, known as “transgenerational epigenetic inheritance,” is now the focus of intense scientific investigation.

For many years, it was thought that sperm do not retain any histone packaging and therefore could not transmit histone-based epigenetic information to offspring. Recent studies, however, have shown that about 10 percent of histone packaging is retained in both human and mouse sperm.

“Furthermore, where the chromosomes retain histone packaging of DNA is in developmentally important regions, so those findings raised awareness of the possibility that sperm may transmit important epigenetic information to embryos,” Strome said.

When her lab looked at C. elegans sperm, they found the sperm genome fully retains histone packaging. Other researchers had found the same is true for another commonly studied organism, the zebrafish.

“Like zebrafish, worms represent an extreme form of histone retention by sperm, which makes them a great system to see if this packaging really matters,” Strome said.

Her lab focused on a particular epigenetic mark (designated H3K27me3) that has been well established as a mark of repressed gene expression in a wide range of organisms. The researchers found that removing this mark from sperm chromosomes causes the majority of the offspring to be sterile. Having established that the mark is important, they wanted to see if it is sufficient to guide normal germline development.

The researchers addressed this by analyzing a mutant worm in which the chromosomes from sperm and egg are separated in the first cell division after fertilization, so that one cell of the embryo inherits only sperm chromosomes and the other cell inherits only egg chromosomes (normally, each cell of an embryo inherits chromosomes from both egg and sperm). This unusual chromosome segregation pattern allowed the researchers to generate worms whose germ line inherited only sperm chromosomes and therefore only sperm epigenetic marks. Those worms turned out to be fertile and to have normal gene expression patterns.

“These findings show that the DNA packaging in sperm is important, because offspring that did not inherit normal sperm epigenetic marks were sterile, and it is sufficient for normal germline development,” Strome said.

While the study shows that epigenetic information transmitted by sperm is important for normal development, it does not directly address how the life experience of a father can affect the health of his descendants. Strome’s lab is investigating this question with experiments in which worms are treated with alcohol or starved before reproducing.

“The goal is to analyze how the chromatin packaging changes in the parent,” she said.

“Whatever gets passed on to the offspring has to go through the germ cells. We want to know which cells experience the environmental factors, how they transmit that information to the germ cells, what changes in the germ cells, and how that impacts the offspring.”

By demonstrating the importance of epigenetic information carried by sperm, the current study establishes that if the environment experienced by the father changes the epigenetics of sperm chromosomes, it could affect the offspring.

Continue Reading

News

Father’s Nicotine Use Can Cause Cognitive Problems In Children And Grandchildren

Published

on

By

A father’s exposure to nicotine may cause cognitive deficits in his children and even grandchildren, according to a study in mice publishing on October 16 in the open-access journal PLOS Biology by Pradeep Bhide of Florida State University in Tallahassee and colleagues. The effect, which was not caused by direct secondhand exposure, may be due to epigenetic changes in key genes in the father’s sperm.

Exposure of mothers to nicotine and other components of cigarette smoke is recognized as a significant risk factor for behavioral disorders, including attention deficit hyperactivity disorder, (or ADHD) in multiple generations of descendants. Whether the same applies to fathers has been less clear, in part because in human studies it has been difficult to separate genetic factors (such as a genetic predisposition to ADHD) from environmental factors, such as direct exposure to cigarette smoke.

To overcome this difficulty, Deirdre McCarthy, Pradeep Bhide and colleagues exposed male mice to low-dose nicotine in their drinking water during the stage of life in which the mice produce sperm. They then bred these mice with females that had never been exposed to nicotine. While the fathers were behaviorally normal, both sexes of offspring displayed hyperactivity, attention deficit, and cognitive inflexibility. When female (but not male) mice from this generation were bred with nicotine-naïve mates, male offspring displayed fewer, but still significant, deficits in cognitive flexibility. Analysis of spermatozoa from the original nicotine-exposed males indicated that promoter regions of multiple genes had been epigenetically modified, including the dopamine D2 gene, critical for brain development and learning, suggesting that these modifications likely contributed to the cognitive deficits in the descendants.

Nicotine and cigarette smoke have been previously shown to cause widespread epigenetic changes, Bhide said.

“The fact that men smoke more than women makes the effects in males especially important from a public health perspective. Our findings underscore the need for more research on the effects of smoking by the father, rather than just the mother, on the health of their children.”

Continue Reading

News

Nutrition Has A Greater Impact On Bone Strength Than Exercise

Published

on

ANN ARBOR—One question that scientists and fitness experts alike would love to answer is whether exercise or nutrition has a bigger positive impact on bone strength. University of Michigan researchers looked at mineral supplementation and exercise in mice, and found surprising results–nutrition has a greater impact on bone mass and strength than exercise. Further, even after the exercise training stopped, the mice retained bone strength gains as long as they ate a mineral-supplemented diet.

“The longer-term mineral-supplemented diet leads to not only increases in bone mass and strength, but the ability to maintain those increases even after detraining,” said David Kohn, a U-M professor in the schools of dentistry and engineering.

“This was done in mice, but if you think about the progression to humans, diet is easier for someone to carry on as they get older and stop exercising, rather than the continuation of exercise itself.”

The second important finding is that the diet alone has beneficial effects on bone, even without exercising. This surprised Kohn, who expected exercise with a normal diet to fuel greater gains in bone strength, but that wasn’t the case.

“The data suggests the long-term consumption of the mineral-supplemented diet could be beneficial in preventing the loss of bone and strength with age, even if you don’t do exercise training,” he said.

Combining the two amplifies the effect.

Most other studies look at effects of increasing dietary calcium, Kohn said. The U-M study increased calcium and phosphorous, and found benefits to increasing both.

This isn’t to suggest that people run out and buy calcium and phosphorus supplements, Kohn said. The findings don’t translate directly from mice to humans, but they do give researchers a conceptual place to start.

It’s known that humans achieve peak bone mass in their early 20s, and after that it declines. The question becomes how to maximize the amount of bone when young, so that when declines do begin, people start from a better position, Kohn said.

In addition to testing bone mass and strength, Kohn and colleagues performed a full battery of mechanical assessments on the bone, which is important because the amount of bone doesn’t always scale with or predict the mechanical quality of the tissue.

They tested the mice after eight weeks of training and supplemented diet or normal diet, and then after eight weeks of detraining.

Continue Reading

Like Us on Facebook

Trending Posts

News3 days ago

Paternal Transmission Of Epigenetic Memory Via Sperm

Studies of human populations and animal models suggest that a father’s experiences such as diet or environmental stress can influence...

News3 days ago

Father’s Nicotine Use Can Cause Cognitive Problems In Children And Grandchildren

A father’s exposure to nicotine may cause cognitive deficits in his children and even grandchildren, according to a study in...

News3 days ago

Nutrition Has A Greater Impact On Bone Strength Than Exercise

ANN ARBOR—One question that scientists and fitness experts alike would love to answer is whether exercise or nutrition has a...

News3 days ago

Breast­feed­ing Pro­tects In­fants From An­ti­bi­otic-Res­ist­ant Bac­teria

Globally, more than 200,000 newborns die annually of infections caused by antibiotic-resistant bacteria. However, a new study shows that breastfeeding...

News3 days ago

Combining Genetic and Sun Exposure Data Improves Skin Cancer Risk

SAN DIEGO, Calif. – By combining data on individuals’ lifetime sun exposure and their genetics, researchers can generate improved predictions...

News5 days ago

More Clues Revealed In Link Between Normal Breast Changes And Invasive Breast Cancer

A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process —...

News5 days ago

Kids’ Sleep May Suffer From Moms’ Tight Work Schedules

It may be tough for working moms to get a good night’s sleep, but working tight hours may affect their...

Trending