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Sex-specific effects on elements of the social brain neural network in Wistar rats from perinatal exposure to
Stacy Schkoda1, Brian Horman1, Shannah Witchey1
1Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, United States.
Insights
Developmental exposure to flame retardants (FRs) alters neurobehavior. In female rats, FRs disrupted serotonin and estrogen receptor α (ERα) in brain regions linked to socioemotional behaviors.
Area of Science:
- Environmental toxicology
- Neuroscience
- Developmental toxicology
Background:
- Developmental exposure to chemical flame retardants (FRs) is associated with neurodevelopmental disorders and socioemotional deficits.
- Previous studies showed gestational/lactational exposure to FR mixture Firemaster 550 (FM 550) or its components caused anxiety and reduced sociality in rats.
Purpose of the Study:
- To investigate sex- and chemical-specific disruptions in brain regions underlying behavioral changes induced by developmental FR exposure.
- To identify molecular targets in brain regions associated with anxiety and social behavior.
Main Methods:
- Wistar rats were exposed to FM 550 or its organophosphate ester (OPFR) components during gestation and lactation.
- Offspring underwent immunohistochemistry and autoradiography at postnatal day 90 to assess serotonin, estrogen receptor α (ERα), and oxytocin receptor (OTR) expression.
- Analysis focused on brain regions including the medial amygdala and bed nucleus of the stria terminalis (BNST).
Main Results:
- No significant effects were observed in males for any measured biological target.
- Female rats exposed to FM 550 showed increased serotonin innervation in the medial amygdala.
- FM 550 and OPFR exposure reduced ERα expression in the BNST of females.
- Exploratory findings suggested disrupted OTR in males, particularly in the BNST.
Conclusions:
- Developmental exposure to FRs causes sex-specific alterations in neurochemical signaling and receptor expression in the brain.
- These molecular changes in key brain regions may underlie the observed socioemotional behavioral deficits.
- Findings provide insights into the mechanisms by which FRs contribute to neurodevelopmental and socioemotional disorders.
Abstract:
Developmental exposure to chemical flame retardants (FRs) has been linked to a variety of neurodevelopmental disorders and abnormal socioemotional behaviors in human and laboratory animal studies. We have previously shown in Wistar rats that gestational and lactational exposure to the FR mixture Firemaster 550 (FM 550) or its brominated or organophosphate ester (OPFR) components (at 2000 µg, 1000 µg, and 1000 µg oral to the dam respectively (absolute and not by bodyweight)) results in increased anxiety-like behaviors in females and decreased sociality in both sexes. Using their siblings, this study characterized sex and chemical specific targets of disruption in brain regions underlying each behavioral phenotype. Offspring were exposed across gestation and lactation then prepared for either immunohistochemistry or autoradiography at postnatal day 90 to quantify expression of serotonin, estrogen receptor α (ERα), and oxytocin receptor (OTR) in multiple brain regions. No effect of exposure was found in males for any biological target. In females, serotonin innervation was increased in the medial amygdala of FM 550 exposed animals while ERα expression in the bed nucleus of the stria terminalis (BNST) was reduced by FM 550 and OPFR. Evidence of disrupted OTR was observed in males, particularly the BNST but considered an exploratory finding given the small sample size. These results begin to shed light on the mechanisms by which developmental FR exposure alters socioemotional behaviors of relevance to neurodevelopmental disorders.
