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

Daniel G. Kougias, Elli P. Sellinger, Jari Willing, Janice M Juraska

Research output: Contribution to journalArticle

Abstract

The growth and organization of the developing brain are known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, such as 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/d through pregnancy and for 10 d 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.

Original languageEnglish (US)
Pages (from-to)6864-6872
Number of pages9
JournalJournal of Neuroscience
Volume38
Issue number31
DOIs
StatePublished - Aug 1 2018

Fingerprint

Prefrontal Cortex
Synapses
Neurons
Hormones
Executive Function
Brain
Lactation
Neuroglia
Placenta
phthalic acid
Pathology
Pregnancy
Growth

Keywords

  • Attentional set shift
  • Endocrine disruptor
  • Neuron number
  • Phthalates
  • Synapse number
  • mPFC

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "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",
abstract = "The growth and organization of the developing brain are known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, such as 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/d through pregnancy and for 10 d 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.",
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