You are here:
ONTOGENETIC ALTERATIONS IN MOLECULAR AND STRUCTURAL CORRELATES OF DENDRITIC GROWTH FOLLOWING DEVELOPMENTAL EXPOSURE TO POLYCHLORINATED BIPHENYLS.
Citation:
LEIN, P. J., D. YANG, A. D. BACHSTETTER, H. A. TILSON, G. J. HARRY, R. F. MERVIS, AND PRASADA RAO S. KODAVANTI. ONTOGENETIC ALTERATIONS IN MOLECULAR AND STRUCTURAL CORRELATES OF DENDRITIC GROWTH FOLLOWING DEVELOPMENTAL EXPOSURE TO POLYCHLORINATED BIPHENYLS. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 115(4):556-563, (2007).
Impact/Purpose:
To examine whether disruption of neuronal connectivity contributes to neuropsychological deficits seen in children exposed to PCBs
Description:
This is the first report showing both molecular and structural changes in brain following developmental exposure to a neurotoxicant. It is known that perinatal exposure to a neurotoxicant, 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. Rats were exposed in utero and throughout lactation via oral gavage of dams with vehicle (corn oil) or the commercial PCB mixture Aroclor 1254 (6 mg/kg/d) from gestational day 6 through postnatal day (PND) 21. Golgi analyses of CA1 hippocampal pyramidal neurons indicated that PCBs decreased dendritic branching and spine density at PND22, but increased dendritic branching by PND60 while spine density was unchanged relative to age-matched controls. In cerebellar Purkinje cells, the dendritic area was reduced by PCBs at PND22 but comparable to control levels by PND60. PCB exposure did not change spine density in Purkinje cells at either age. Quantitative RT-PCR analyses demonstrated that PCBs tended to shift the developmental profile of spinophilin and RC3/neurogranin to the left in postnatal brains. In the hippocampus, this shift was evident from PND14 through PND56; in the cortex, significant increases were observed at PND7 through PND21; and in the cerebellum, spinophilin mRNA levels were not altered while RC3/neurogranin levels were significantly increased at PND4 and PND21. 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.