Papers of the Month
By Mali Velasco
Flame retardants decrease immune response in children with autism
Exposure to polybrominated diphenyl ethers (PBDEs) may suppress immune response in children with autism, according to an NIEHS-funded study. Autism is a neurological and developmental disorder that affects approximately one in 36 children in the U.S. Although the overall cause of the disorder is unknown, emerging research has linked changes to the immune system with increased neurodevelopmental deficits.
PBDEs include more than 200 chemicals used in furniture, electronics, and building materials to prevent burning or slow the spread of fire. These chemicals can accumulate in the environment and can interfere with normal immune and neurological development.
The researchers analyzed blood samples from 93 children, including children diagnosed with and without autism. Specifically, they examined the effect of concentrations of 14 PBDE chemicals on T cells, a type of white blood cell that establishes and maintains immune responses. The researchers measured similar PBDE concentrations in both groups. However, they found associations between several PBDE chemicals and reduced T-cell function only in children with autism.
Next, the team exposed participants’ blood cells to BDE-49, a type of PBDE known for its high neurotoxicity. They found that BDE-49 exposure increased the production of cytokines and chemokines — proteins associated with inflammation and neurodegeneration — by immune cells. In addition, they found the level of BDE-49 necessary to negatively affect cytokines and chemokines was lower than those of other PBDEs.
According to the authors, PBDEs have a more detrimental effect on the immune responses of children with autism, and the toxicant BDE-49 may be specifically damaging to the immune system.
Citation: Akintunde ME, Lin YP, Krakowiak P, Pessah IN, Hertz-Picciotto I, Puschner B, Ashwood P, Van de Water J. 2023. Ex vivo exposure to polybrominated diphenyl ether (PBDE) selectively affects the immune response in autistic children. Brain Behav Immun Health 34:100697.
Culinary-inspired technique removes arsenic from water
A new approach developed by NIEHS-funded researchers improved the ability of carbon-based filters to remove arsenic from drinking water. This method, which is inspired by a cooking technique known as sous vide, may offer a cheaper and more practical solution to prevent arsenic exposure.
The study builds on an earlier finding that adding titanium hydroxide particles within filters called carbon blocks can trap arsenic. The filters are commonly used in point-of-use water filtration systems — such as those under the sink and in refrigerators — to remove unwanted tastes, odors, and bacteria. They are also used to remove organic contaminants but not metals like arsenic.
To ensure that the titanium particles are evenly distributed in the filter and do not affect water flow, the researchers used an approach similar to cooking food in a water-filled, vacuum-sealed container. In short, they added the carbon block filter to a flexible pouch and removed air using a vacuum, added a titanium solution into the pouch, sealed the pouch to keep air out, and heated it in a hot water bath.
Next, the researchers tested the filter’s ability to remove two common forms of arsenic — arsenate and arsenite — from contaminated tap water samples. They found that the device efficiently removed both types of arsenic, at levels as low as 10 micrograms per liter and as high as 100 micrograms per liter.
According to the authors, the technique uses 70% fewer chemicals and is more affordable than other methods currently available for removing arsenic from drinking water, offering a new solution to reduce exposures.
Citation: Farsad A, Marcos-Hernandez M, Sinha S, Westerhoff P. 2023. Sous vide-inspired impregnation of amorphous titanium (hydr)oxide into carbon block point-of-use filters for arsenic removal from water. Environ Sci Technol 57(48):20410–20420.
Rapid-imaging method leverages machine learning to study immune cells
A team of university- and small business-based researchers partly funded by NIEHS developed a new approach that combines advanced imaging methods with machine learning to rapidly image and count neutrophils, a type of immune cell, in zebrafish embryos. Research suggests that exposure to environmental pollutants can decrease neutrophil levels, emphasizing the need for strategies to screen chemicals affecting neutrophil counts.
Zebrafish are commonly used to study immunity because their embryos are transparent, allowing researchers to label neutrophils with fluorescent tags and count them. However, current methods to image and quantify neutrophils are time-consuming. To address this challenge, the team developed a device called a Multi-Camera Array Microscope. The tool combines numerous mini-microscopes, which provide a flexible viewing area, with a data processing software used in immune cell studies.
To test their device, the researchers bred zebrafish that expressed fluorescent neutrophils and placed one embryo in each well of a 96-well plate. Using the Multi-Camera Array Microscope, they captured 18 billion pixels across the well plates in 75 seconds. Then, harnessing an algorithm developed through machine learning, they processed the imaging data in five minutes to determine the number of individual fluorescent neutrophils in each embryo.
Compared to neutrophil counts made by hand, the team’s method was as effective and took significantly less time — 6.25 minutes total compared with 45 minutes for the manual method.
The open-source software package can be modified for studies involving other zebrafish cell lines and can be adapted for use with other cell types in other organisms, according to the authors.
Citation: Efromson J, Ferrero G, Bègue A, Doman TJJ, Dugo C, Barker A, Saliu V, Reamey P, Kim K, Harfouche M, Yoder JA. 2023. Automated, high-throughput quantification of EGFP-expressing neutrophils in zebrafish by machine learning and a highly-parallelized microscope. PLoS One. 18(12):e0295711.
Identifying causes, potential interventions for radiation-induced neurotoxicity
NIEHS-funded scientists identified how radiation therapy can damage brain cells, providing new insights into the major cellular drivers of radiation neurotoxicity and associated cognitive problems. External beam radiotherapy is used to treat brain tumors; however, the doses required to treat tumors can damage brain cells and cause memory and learning issues, especially in young children.
To identify the mechanisms underlying neurotoxicity, the researchers exposed newborn, adolescent, juvenile, and adult mice to low and high levels of radiation. Following exposure, they conducted several neurobehavioral tests and found that the ability of mice to learn and remember worsened after radiation exposure at both high and low doses, particularly among younger mice. Analysis of brain cells from young mice showed dying neurons in areas involved in learning. Three types of brain cells critical for proper brain function — progenitor cells, neurons, and astrocytes — were also found to die after radiation through a process called apoptosis.
Further analysis of individual brain cells revealed that young mice had higher levels of proteins that could trigger cell apoptosis, including the protein BAX. Blocking BAX activity prevented radiation-induced brain cell death in young mice and prevented memory and learning problems from developing.
These findings suggest that radiation treatment activates certain proteins involved in cell death, damaging parts of the brain involved in learning, particularly among younger individuals. According to the authors, treatment strategies that block apoptosis are needed.
Citation: Singh R, Yu S, Osman M, Inde Z, Fraser C, Cleveland AH, Almanzar N, Lim CB, Joshi GN, Spetz J, Qin XP, Toprani SM, Nagel Z, Hocking MC, Cormack RA, Yock TI, Miller JW, Yuan ZM, Gershon T, Sarosiek KA. 2023. Radiotherapy-induced neurocognitive impairment is driven by heightened apoptotic priming in early life and prevented by blocking BAX. Cancer Res 83(20):3442–3461.