Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: developmental effects.
The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive development, causes psychomotor difficulties, and contributes to attention deficits in children, all of which seem to be associated with altered patterns of neuronal connectivity. In the present study, we examined gene expression profiles in the rat nervous system following PCB developmental exposure. Pregnant rats (Long-Evans) were dosed perinatally with 0 or 6 mg/kg/day of Aroclor 1254 from gestation day 6 through postnatal day (PND) 21. Gene expression in cerebellum and hippocampus from PND7 and PND14 animals was analyzed with an emphasis on developmental aspects. Changes in gene expression (> or =1.5 fold) in control animals identified normal developmental changes. These basal levels of expression were compared to data from Aroclor 1254-treated animals to determine the impact of gestational PCB exposure on developmental parameters. The results indicate that the expression of a number of developmental genes related to cell cycle, synaptic function, cell maintenance, and neurogenesis is significantly altered from PND7 to PND14. Aroclor 1254 treatment appears to dampen the overall growth-related gene expression levels in both regions with the effect being more pronounced in the cerebellum. Functional analysis suggests that Aroclor 1254 delays maturation of the developing nervous system, with the consequences dependent on the ontological state of the brain area and the functional role of the individual gene. Such changes may underlie learning and memory deficits observed in PCB exposed animals and humans.
Royland
Joyce E
JE
Neurotoxicology Divisions, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Wu
Jinfang
J
Zawia
Nasser H
NH
Kodavanti
Prasada Rao S
PR
D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D018811:Maternal Exposure; D009498:Neurotoxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D009435:Synaptic Transmission / Q000187:drug effects
D013956:Antithyroid Agents; D009498:Neurotoxins; D020111:Chlorodiphenyl (54% Chlorine)