Ontogenetic Alterations in Molecular and Structural Correlates of Dendritic Growth after Developmental Exposure to Polychlorinated Biphenyls

• Published in: Environmental health perspectives Vol. 115; no. 4; pp. 556 - 563
• Main Authors: Lein, Pamela J., Yang, Dongren, Adam D. Bachstetter, Tilson, Hugh A., Harry, G. Jean, Ronald F. Mervis, Prasada Rao S. Kodavanti
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01.04.2007; National Institute of Environmental Health Sciences
• Subjects: Animals; Brain; Cell Enlargement; Cerebellum; Child; Cognition Disorders - chemically induced; Dendritic cells; Dendritic Cells - drug effects; Dendritic spines; Developmental Disabilities - chemically induced; Disease Models, Animal; Environmental Pollutants - toxicity; Female; Genetic aspects; Health aspects; Hippocampus; Humans; Influence; Messenger RNA; Neural networks; Neurons; Polychlorinated biphenyls; Polychlorinated Biphenyls - toxicity; Pregnancy; Prenatal Exposure Delayed Effects; Psychological aspects; Purkinje cells; Purkinje Cells - drug effects; Pyramidal Tracts - cytology; Pyramidal Tracts - drug effects; Rats; Rats, Long-Evans; Thyroid hormones; United States
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.9773

Objective: Perinatal exposure to polychlorinated biphenyls (PCBs) is associated with decreased IQ scores, impaired learning and memory, psychomotor difficulties, and attentional deficits in children. It is postulated that these neuropsychological deficits reflect altered patterns of neuronal connectivity. To test this hypothesis, we examined the effects of developmental PCB exposure on dendritic growth. Methods: Rat dams were gavaged from gestational day 6 through postnatal day (PND) 21 with vehicle (corn oil) or the commercial PCB mixture Aroclor 1254 (6 mg/kg/day). Dendritic growth and molecular markers were examined in pups during development. Results: Golgi analyses of CA1 hippocampal pyramidal neurons and cerebellar Purkinge cells indicated that developmental exposure to PCBs caused a pronounced age-related increase in dendritic growth. Thus, even though dendritic lengths were significantly attenuated in PCB-treated animals at PND22, the rate of growth was accelerated at later ages such that by PND60, dendritic growth was comparable to or even exceeded that observed in vehicle controls. Quantitative reverse transcriptase polymerase chain reaction analyses demonstrated that from PND4 through PND21, PCBs generally increased expression of both spinophilin and RC3/neurogranin mRNA in the hippocampus, cerebellum, and cortex with the most significant increases observed in the cortex. Conclusions: This study demonstrates that developmental PCB exposure alters the ontogenetic profile of dendritogenesis in critical brain regions, supporting the hypothesis that disruption of neuronal connectivity contributes to neuropsychological deficits seen in exposed children.