Neurodevelopmental and behavioral toxicity via lactational exposure to the sum of six indicator non-dioxin-like-polychlorinated biphenyls (∑6 NDL-PCBs) in mice

• Published in: Toxicology (Amsterdam) 2012-09, Vol.299 (1), p.44-54
• Main Authors: Elnar, Arpiné Ardzivian, Diesel, Britta, Desor, Frédéric, Feidt, Cyril, Bouayed, Jaouad, Kiemer, Alexandra K, Soulimani, Rachid
• Format: Article
• Language: English
• Subjects: 6 NDL-PCBs; adults; adverse effects; Animals; Animals, Newborn; Anxiety; Behavior; Behavior, Animal - drug effects; Biological and medical sciences; Brain - drug effects; Brain - metabolism; calcium signaling; cerebellum; Chemical and industrial products toxicology. Toxic occupational diseases; cognition; Development; Emergency; emotions; Female; fish; gamma-Aminobutyric Acid - genetics; gamma-Aminobutyric Acid - metabolism; gene expression; lactating women; Lactation; Life Sciences; locomotion; Male; males; Maternal Exposure - adverse effects; Medical sciences; messenger RNA; Mice; mothers; Motor Activity - drug effects; neonates; neurodevelopment; neurons; Neurotoxicity; Polychlorinated Biphenyls - administration & dosage; Polychlorinated Biphenyls - toxicity; progeny; Random Allocation; Receptors, Opioid, mu - genetics; Receptors, Opioid, mu - metabolism; reflexes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - chemistry; RNA, Messenger - genetics; Ryanodine Receptor Calcium Release Channel - genetics; Ryanodine Receptor Calcium Release Channel - metabolism; RyR3; Serotonin - genetics; Serotonin - metabolism; Statistics, Nonparametric; toxicity; Toxicology; Various organic compounds
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2012.05.004

Abstract In this study, the neurobehavioral toxicity of lactational exposure to a representative mixture of the six indicator non-dioxin-like-polychlorinated biphenyls (∑6 NDL-PCBs 28, 52, 101, 138, 153 and 180) found in contaminated fish matrices were assessed in neonatal (postnatal day 0) to adult (postnatal day 275) mice. Thus, a battery of developmental, behavioral and cognitive tests was performed. The performance of mice whose mothers were orally exposed to ∑6 NDL-PCBs at environmental doses of 1 ng/kg, 10 ng/kg or 100 ng/kg was compared to that of mice whose mothers were orally exposed to vehicle. Our results showed that neonatal offspring mice exposed to ∑6 NDL-PCBs through lactation exhibited significantly longer turning reflexes on postnatal days 7 and 9 ( p = 0.001, p = 0.002, respectively) at 100 ng/kg and showed a reduction in their general activity at 1 ng/kg ( p = 0.002) and 10 ng/kg ( p = 0.001) compared to controls. However, these developmental alterations were sex-dependent; only the female reflexes and male locomotor activity were affected. These disturbances were transient, and they disappeared with age. In addition, the males’ visuomotor integration was also altered at the doses of 1 ng/kg ( p = 0.02) and 100 ng/kg ( p = 0.004), as revealed by the WESPOC test. Nevertheless, lactational exposure to ∑6 NDL-PCBs (1–100 ng/kg) resulted in persistent disturbances despite a long post-weaning period; the exposed mice exhibited anxious behavior that was detected at more progressive life stages, i.e., at postnatal days 40 and 160, using an elevated plus maze and the light/dark choice test, respectively. This persistent anxious behavior could be related to the overexpression of RyR3 in the cerebellum via the disruption of calcium signaling in the neurons. We found no differences in the offspring mice with regard to their cognitive function and mood or mRNA neurotransmitter receptor gene expression in several brain areas, including 5-HT1A , MOR1 and GABAAα1 , suggesting the absence of adverse effects of postnatal exposure to ∑6 NDL-PCBs under these conditions. Therefore, our results suggest that regular consumption of contaminated fish matrices by lactating women could be detrimental to the neurodevelopment of their newborns.