Papers of the Month
By Megan Avakian
Harmful algal toxin changes zebrafish neurodevelopment
Low-dose exposure to domoic acid in early life altered zebrafish neurodevelopment and behavior, according to new NIEHS-funded research. The study sheds light on the mechanisms by which domoic acid affects the developing nervous system and identifies a window of susceptibility to exposure. Domoic acid is a neurotoxic compound produced by certain harmful algae. Humans are primarily exposed through eating contaminated seafood.
Domoic acid was injected into zebrafish at 1 to 4 days post fertilization (dpf), including distinct neurodevelopmental timepoints. At 5 dpf, the researchers used imagining techniques to examine the myelin sheath, which is important for proper transmission of nerve signals throughout the body. Using genetic sequencing methods, they identified altered gene expression resulting from exposure at 2 dpf. They performed behavioral tests at 7 dpf to determine the functional impact of exposure.
Fish exposed to domoic acid at 2 dpf, but not 1 or 4 dpf, showed consistent deficits in behavior, including lower responsiveness to stimuli. Similarly, only fish exposed at 2 dpf showed myelin sheath defects. Exposure at 2 dpf decreased expression of genes required for maintaining myelin sheath and nerve structure.
According to the authors, these results reveal a critical window of susceptibility to domoic acid exposure in zebrafish and identify altered gene expression and myelin structure as possible mechanisms driving behavioral deficits.
Citation: Panlilio JM, Aluru N, Hahn ME. 2020. Developmental neurotoxicity of the harmful algal bloom toxin domoic acid: cellular and molecular mechanisms underlying altered behavior in the zebrafish model. Environ Health Perspect 128(11):117002.
Childhood lead exposure affects midlife brain
Children exposed to lead have altered brain structure and poorer cognitive function in midlife, according to NIEHS-funded research. These lead-related brain changes may increase the risk of neurodegenerative disease, like dementia, in later life.
The study included 564 children who were enrolled in a New Zealand birth cohort in the early 1970s and followed to midlife. The researchers measured child blood lead levels at age 11 years. Using magnetic resonance imaging, they examined participants’ structural brain integrity at age 45 years. They also assessed adult cognitive function and intelligence using a standardized IQ test.
Higher lead exposure in childhood was associated with structural deficits in the middle-aged brain. High child blood lead levels were linked to reduced volumes of gray and white matter in the brain, which are important for learning, memory, and communication between brain regions. Participants with higher blood lead as children also scored lower in IQ tests in midlife. Specifically, for each 5 micrograms per deciliter more lead they carried as children, study participants lost an average of 2 IQ points by age 45.
According to the authors, results suggest that adults exposed to lead as children may be at increased risk of neurodegenerative diseases in later life and reinforce the need for long-term follow-up of lead exposed child cohorts.
Citation: Reuben A, Elliott ML, Abraham WC, Broadbent J, Houts RM, Ireland D, Knodt AR, Poulton R, Ramrakha S, Hariri AR, Caspi A, Moffitt TE. 2020. Association of childhood lead exposure with MRI measurements of structural brain integrity in midlife. JAMA 324(19):1970–1979.
Air pollution exposure in pregnancy and maternal bone strength
NIEHS grantees identified a link between air pollution exposure during pregnancy and diminished maternal bone strength. This study is the first to examine the association between fine particulate matter (PM2.5) and bone strength in pregnant women. Bone strength is known to decline during pregnancy and recover after birth. Pollution exposures may worsen this loss, potentially increasing risk of fracture.
The study included 930 pregnant women enrolled in a long-term study in Mexico City. Using a spatiotemporal model based on participant addresses, the researchers estimated daily ambient PM2.5 exposure from 60 days before conception to six months postpartum. They used bone ultrasound to measure bone strength in mid- and late pregnancy and up to six months postpartum.
High ambient PM2.5 exposure was associated with lower bone strength two to three months after exposure. For example, PM2.5 exposure in early pregnancy was associated with diminished bone strength in the second and third trimesters. This relationship weakened over time, with bone strength loss becoming less pronounced in the postpartum period. The researchers observed similar bone loss patterns for PM2.5 exposures in late pregnancy and early postpartum.
According to the authors, technologies and policies aimed at reducing air pollution could improve public health by reducing bone fracture risk.
Citation: Wu H, Kioumourtzoglou M-A, Just AC, Kloog I, Sanders A, Svensson K, McRae N, Tamayo-Ortiz M, Solano-Gonzalez M, Wright RO, Tellez-Rojo MM, Baccarelli AA. 2020. Association of ambient PM2.5 exposure with maternal bone strength in pregnant women from Mexico City: a longitudinal cohort study. Lancet Planet Health 4(11):e530–e537.
Children’s gut microbiome linked with household chemical exposure
Exposure to semi-volatile organic compounds (SVOCs) was linked with changes to young children’s gut microbiome, according to a new NIEHS-funded study. SVOCs are common contaminants of indoor air and dust. Young children are especially vulnerable to exposure through dust because they spend time on the floor and frequently put hands and objects in their mouths.
The researchers measured levels of 44 SVOCs, including phthalates and per- and polyfluoroalkyl substances (PFAS), in the blood and urine of 69 children aged 3 to 6 years. Using genetic sequencing techniques, they determined the types and abundance of bacteria and fungi present in child stool samples.
Children with higher levels of PFAS in their blood had a lower number and diversity of bacteria in their gut. Higher phthalate levels were associated with a reduction in gut fungal populations. Surprisingly, children with higher levels of certain SVOCs, including triclosan, had several types of bacteria in their gut known to break down toxic chemicals in the environment. These bacteria are not typically found in the human gut. This finding suggested that exposure to SVOCs may act as a selective pressure in the developing gut to increase the abundance of microbes that can tolerate or metabolize the compounds.
Citation: Gardner CM, Hoffman K, Stapleton HM, Gunsch CK. 2020. Exposures to semivolatile organic compounds in indoor environments and associations with the gut microbiomes of children. Environ Sci Technol Lett; doi:10.1021/acs.estlett.0c00776 [Online 2 Nov 2020].
(Megan Avakian is a science writer for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)