Social recognition deficits after developmental exposure to indoor flame retardants are correlated with an altered amygdala‐prefrontal cortex circuit and expression of social neuropeptides
Authors: Kozlova Elena V. , Carrillo Valeria , Denys Maximillian , Lampel Gregory , Bishay Anthony , Monarrez Eduardo , Curras-Collazo Margarita C. , rabanni Kayhon 
Published: April 2020

Polybrominated diphenyl ethers (PBDEs) are indoor flame retardant pollutants with adverse neurobehavioral effects. In humans, PBDEs are associated with hyperactivity and impairments in executive function, psychomotor and mental development, attention and social competence. There is evidence showing that early‐life PBDE exposure, coinciding with critical developmental periods can permanently alter brain processes and behavior. Our lab has found that perinatal exposure to DE‐71, an industrial mixture of PBDEs, produces a behavior phenotype displaying altered social recognition ability and anxiety. This study further evaluates long‐term social recognition ability, and correlative changes in olfaction, gene expression of prosocial peptides, oxytocin and vasopressin and their receptors, and connectivity in the basolateral amygdala‐prefrontal cortex (BLA‐PFC), a critical component of the social brain network. C57BL/6 dams were dosed with DE‐71 for 10 wk (pre‐conception: 4 wk; gestation: 3 wk; lactation: 3 wk). Dosing consisted of low dose (LD, 0.1 mg/kg/d), high dose (HD, 0.4 mg/kg/d), or corn oil vehicle control (OD) administered via ingestion of infused corn flakes. Exposed progeny were subjected to behavioral testing for short‐ and long‐term social memory (social recognition task‐SRT, social memory recognition test‐SMRT), social novelty (sociability‐SOC), olfaction and anxiety (elevated plus maze‐EPM, Suok). When compared to OD controls, LD and HD male and female offspring exhibited deficits in short‐term SRT ability relative to OD, showing no preference to investigate a novel versus familiar mouse. LD males and females also showed long‐term social recognition memory deficits. In LD males and females this may be due to altered ability to discriminate two social odors as measured by an olfactory habituation/dishabituation (OHT). On EPM, LD males showed significantly more time spent in open arm indicating less anxiety while the opposite was found in HD female. Adult exposure in LD and HD dams did not produce altered SRT or OHT behavior. Gene markers of central vasopressin (Avp, Avp1ar) and oxytocin system (Oxt, Oxtr) were examined in offspring brains using qRT‐PCR. In HD females we found reduced Avp in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus and reduced Avp1ar expression in the SON.To investigate potential alterations to the BLA‐PFC circuit that may underlie DE‐71‐induced deficits in social recognition, Cholera Toxin B was injected into the prelimbic cortex at PND30 and labeled PFC‐projecting BLA neurons were stereologically quantified. Significantly more labeled neurons (normalized to total cells) were found in the BLA of LD and HD males. In summary, perinatal exposure to DE‐71 may reprogram forebrain neurodevelopment and hypothalamic neurochemistry of “social” peptides possibly leading to altered prosocial and anxiogenic behavior phenotypes relevant to neurodevelopmental disorders.Support or Funding InformationSigma Xi GIAR (EK, KR), UC MEXUS (EK), UC Minigrant (VC, GL, KR), UCR RISE (MD), APS STRIDE (AB)