| Ontogenetic Alterations in Molecular and Structural Correlates of Dendritic Growth after Developmental Exposure to Polychlorinated Biphenyls Pamela J. Lein,1 Dongren Yang,1 Adam D. Bachstetter,2,3 Hugh A. Tilson,4 G. Jean Harry,5 Ronald F. Mervis,2,3 and Prasada Rao S. Kodavanti4 1Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USA; 2Neurostructural Research Labs, Tampa, Florida, USA; 3Center of Excellence for Aging and Brain Repair and Department of Neurosurgery, University of South Florida College of Medicine, Tampa, Florida, USA; 4Cellular and Molecular Toxicology Branch, Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 5National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Abstract
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. Key words: dendritogenesis, developmental neurotoxicology, learning and memory, molecular markers, polychlorinated biphenyls. Environ Health Perspect 115:556–563 (2007) . doi:10.1289/ehp.9773 available via http://dx.doi.org/ [Online 16 January 2007]
Address correspondence to P.R.S. Kodavanti, Cellular and Molecular Toxicology Branch, Neurotoxicology Division, B 105-06, NHEERL/ORD, U.S. EPA, Research Triangle Park, NC 27711 USA. Telephone: (919) 541-7584. Fax: (919) 541-0717. E-mail: kodavanti.prasada@epa.gov We thank E. Derr-Yellin for the excellent technical assistance, M. Lasarev (OHSU) for assistance with statistical analyses of quantitative reverse transcriptase polymerase chain reaction data, and L. Meserve, C. Wallace, and R.B. Mohammad for manuscript review. This research was supported in part by the intramural research program of the NIEHS, NIH, with primary support from the NHEERL, U.S. EPA. The morphometric work was conducted by R. Mervis under U.S. EPA contract 0D-5558-NANX. This work was partially supported by NIH grants NS046649 (to P.J.L.) and HD40936 (to P.J.L) . The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. EPA, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors declare they have no competing financial interests. Received 29 September 2006 ; accepted 16 January 2007.
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