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June 16, 2017
Digest

Baby Teeth Link Autism and Heavy Metals, Study Suggests

Baby teeth from children with autism contain more toxic lead and less of the essential nutrients zinc and manganese, compared to teeth from children without autism, according to a study funded by NIEHS. The researchers studied twins to control genetic influences and focus on possible environmental contributors to the disease.

The findings, published June 1 in the journal Nature Communications, suggest that differences in early-life exposure to metals, or more importantly how a child’s body processes them, may affect the risk of autism.

Mother and father kissing their baby

The differences in metal uptake between children with and without autism were especially notable during the months just before and after the children were born. The scientists determined this by using lasers to map the growth rings in baby teeth generated during different developmental periods.

The researchers observed higher levels of lead in children with autism throughout development, with the greatest disparity observed during the period following birth. They also observed lower uptake of manganese in children with autism, both before and after birth.

The pattern was more complex for zinc. Children with autism had lower zinc levels earlier in the womb, but these levels then increased after birth, compared to children without autism.

The researchers note that replication in larger studies is needed to confirm the connection between metal uptake and autism.

“We think autism begins very early, most likely in the womb, and research suggests that our environment can increase a child’s risk. But by the time children are diagnosed at age 3 or 4, it’s hard to go back and know what the moms were exposed to,” said Dr. Cindy Lawler, head of the NIEHS Genes, Environment and Health Branch. “With baby teeth, we can actually do that.”

The method of using baby teeth to measure past exposure to metals also holds promise for other disorders, such as attention deficit hyperactivity disorder. “There is growing excitement about the potential of baby teeth as a rich record of a child’s early-life exposure to both helpful and harmful factors in the environment,” said Dr. David Balshaw, head of the NIEHS Exposure, Response and Technology Branch, which supported the development of the tooth method.

Mycobacteria Use Protein to Create Diverse Populations, Avoid Drugs

Subgroups of tuberculosis (TB)-causing bacteria can persist even when antibiotics wipe out most of the overall population. The need to eliminate these persistent subpopulations is one reason why TB treatment regimens are so lengthy. Now, researchers have shown that a single protein allows mycobacteria to generate diverse populations that can avoid TB drugs. The protein may be a target for intervention; blocking it might result in less mycobacterial diversity and shorten TB treatment courses. The research was supported by NIAID and appeared in Nature.

Dr. Eric J. Rubin of Harvard T.H. Chan School of Public Health and Dr. E. Hesper Rego of Yale University School of Medicine and their coworkers first studied Mycobacterium smegmatis, a close relative of Mycobacterium tuberculosis (Mtb), the microbe that causes TB.

Using fluorescent reporter molecules and timelapse microscopy, they examined individual cells as they grew and divided. Mycobacteria can generate daughter cells through asymmetric growth, resulting in genetically identical, but physiologically diverse, populations. The mechanisms underlying this ability and the extent to which the cells’ size, growth rate and other physiological properties relate to survival in mycobacterial populations were not well understood.

Rubin and colleagues determined that the protein product of a single gene, lamA, is a member of the protein machinery that is active when mycobacteria divide. The protein—which is not known to exist in other rod-shaped bacteria or other organisms—seems to allow for asymmetrical growth in new mycobacterial cells made during cell division. The asymmetrical growth leads to bacteria with wide variations in physiological properties and susceptibility to antibiotics.

In experiments using Mtb, the scientists found that mycobacteria without lamA formed far less diverse bacteria with more uniform susceptibility to antibiotics. When exposed to the front-line TB drug rifampicin, for example, Mtb cells lacking lamA were less able to survive than wild-type bacteria. In the future, it may be possible to devise ways to inhibit lamA or its protein. This could lead to reduced variation in Mtb populations and, potentially, to more uniform vulnerability to drugs, according to the scientists.

NIH Researchers Find Potential Genetic Cause of Cushing Syndrome

A small study by researchers at NIH suggests that mutations in the gene CABLES1 may lead to Cushing syndrome, a rare disorder in which the body overproduces the stress hormone cortisol. The study appeared online in Endocrine-Related Cancer.

NIH Researchers Find Potential Genetic Cause of Cushing Syndrome

The excess cortisol found in Cushing syndrome can result from certain steroid medications or from tumors of the pituitary or adrenal glands. Symptoms of the disease include obesity, muscle weakness, fatigue, high blood pressure, high blood sugar, depression and anxiety.

Researchers at NICHD, in collaboration with other institutions in the United States, France and Canada, scanned tumor and cell tissue from 146 children with pituitary tumors evaluated for Cushing syndrome at the Clinical Center. Researchers also scanned the genes of tumors from some of the children. Investigators in France scanned the genes of an additional 35 adult patients with Cushing syndrome and pituitary tumors.

The research team found that four of the patients have mutant forms of CABLES1 that do not respond to cortisol. This is significant because, when functioning normally, the CABLES1 protein, expressed by the CABLES1 gene, slows the division and growth of pituitary cells that produce the hormone adrenocorticotropin (ACTH).

In turn, ACTH stimulates the adrenal gland to produce cortisol, which then acts on the pituitary gland to halt the growth of ACTH-producing cells, effectively suppressing any tumor development. Because cortisol does not affect the four mutant forms of CABLES1 discovered by the researchers, these genes leave production of ACTH-releasing cells unchecked.

“The mutations we identified impair the tumor suppressor function in the pituitary gland,” said the study’s senior author Dr. Constantine Stratakis, director of NICHD’s Division of Intramural Research. “This discovery could lead to the development of treatment strategies that simulate the function of the CABLES1 protein and prevent recurrence of pituitary tumors in people with Cushing syndrome.”

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