Summary: Researchers report rats exposed to phthalates, both while in the womb and through lactation, had fewer neurons and synapses than peers who were not exposed to the plasticizing chemicals. Additionally, the phthalate exposed rats showed deficits in cognitive flexibility.
Source: University of Illinois.
Male and female rats exposed in the womb and during lactation to plasticizing chemicals known as phthalates had significantly fewer neurons and synapses than those that were not exposed, researchers report in a new study. The phthalate-exposed rats had reductions in the size of their medial prefrontal cortex, a brain region that regulates behavior, and showed deficits in cognitive flexibility.
The variety of phthalates and quantities used in the study were environmentally relevant to human exposures, said University of Illinois psychology professor Janice Juraska, who led the research.
“Phthalates are used as plasticizers in a variety of consumer goods, including plastics, personal care products, fragrances, pharmaceuticals, clothing and building materials,” she said. “Contact with these products can lead to exposure through the skin, digestion or lungs.”
Research has shown that phthalates readily cross the placenta to expose a developing fetus, and that they can be delivered to offspring via lactation, Juraska said. Because these chemicals can disrupt normal hormone signaling, their presence in infants and children is of special concern. The developing brain, in particular, is susceptible to hormone disruptions. Several studies in humans suggest that prenatal phthalate exposure may negatively affect children’s behavior, their ability to regulate their own actions and the incidence of neuropsychiatric disorders, she said.
The pregnant rats in the study were each assigned to one of three groups – two of which were exposed to differing concentrations of phthalates during pregnancy and lactation, and one, a control group, that was not exposed at all. The researchers tested how well the offspring learned to use visual and textural cues to navigate a maze, and examined the relative development of their brains once they reached adulthood.
“We found that there was an appreciable reduction in the number of neurons, the number of synapses and the size of the medial prefrontal cortex in the phthalate-exposed rats,” Juraska said. “They also showed a deficit in what we call cognitive flexibility. They made significantly more errors when navigating the mazes than rats that had not been exposed.”
The negative effects of perinatal exposure to phthalates were seen at both doses of the phthalate mixture, the researchers report, which were “presumably within the range of the estimated daily intakes of humans.”
Funding: Juraska is an affiliate of the Beckman Institute for Advanced Science and Technology at Illinois. The National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency supported this research.
Source: Diana Yates – University of Illinois
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Original Research: Abstract for “Perinatal exposure to an environmentally relevant mixture of phthalates results in a lower number of neurons and synapses in the medial prefrontal cortex and decreased cognitive flexibility in adult male and female rats” by Daniel G. Kougias, Elli P. Sellinger, Jari Willing and Janice M. Juraska in Journal of Neuroscience. Published July 16 2018.
Perinatal exposure to an environmentally relevant mixture of phthalates results in a lower number of neurons and synapses in the medial prefrontal cortex and decreased cognitive flexibility in adult male and female rats
The growth and organization of the developing brain is known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, like the medial prefrontal cortex (mPFC). This region is particularly important given its involvement in executive functions and implication in the pathology of many neuropsychiatric disorders. Here, we examine the long-term effects of perinatal exposure to endocrine-disrupting compounds, the phthalates, on the mPFC and associated behavior. This investigation is pertinent as humans are ubiquitously exposed to phthalates through a variety of consumer products and phthalates can readily cross the placenta and be delivered to offspring via lactation. Pregnant dams orally consumed an environmentally relevant mixture of phthalates at 0, 200, or 1000 μg/kg/day through pregnancy and for 10 days while lactating. As adults, offspring were tested in an attentional set-shifting task, which assesses cognitive flexibility. Brains were also examined in adulthood for stereological quantification of the number of neurons, glia, and synapses within the mPFC. We found that, independent of sex, perinatal phthalate exposure at either dose resulted in a reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. Interestingly, the number of synapses was correlated with cognitive flexibility, such that rats with fewer synapses were less cognitively flexible than those with more synapses. These results demonstrate that perinatal phthalate exposure can have long-term effects on the cortex and behavior of both male and female rats.
Humans globally are exposed on a daily basis to a variety of phthalates, which are endocrine-disrupting chemicals. The effects of phthalate exposure on the developing brain, especially on cognitively relevant regions like the medial prefrontal cortex (mPFC), is not known. Here, we use a rat model of human prenatal exposure to an environmentally relevant mixture of phthalates and find there is an appreciable reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. These results may have serious implications for humans given the mPFC is involved in executive functions and is implicated in the pathology of many neuropsychiatric disorders.