Neurobehavioral teratogenicity of perfluorinated alkyls in an avian model.
Perfluorinated alkyls are widely-used agents that accumulate in ecosystems and organisms because of their slow rate of degradation. There is increasing concern that these agents may be developmental neurotoxicants and the present study was designed to develop an avian model for the neurobehavioral teratogenicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Fertilized chicken eggs were injected with 5 or 10mg/kg of either compound on incubation day 0. On the day of hatching, imprinting behavior was impaired by both compounds. We then explored underlying mechanisms involving the targeting of protein kinase C (PKC) isoforms (alpha, beta, gamma) in the intermedial part of the hyperstriatum ventrale, the region most closely associated with imprinting. With PFOA exposure, cytosolic PKC concentrations were significantly elevated for all three isoforms; despite the overall increase in PKC expression, membrane-associated PKC was unaffected, indicating a defect in PKC translocation. In contrast, PFOS exposure evoked a significant decrease in cytosolic PKC, primarily for the beta and gamma isoforms, but again without a corresponding change in membrane-associated enzyme; this likely partial, compensatory increases in translocation to offset the net PKC deficiency. Our studies indicate that perfluorinated alkyls are indeed developmental neurotoxicants that affect posthatch cognitive performance but that the underlying synaptic mechanisms may differ substantially among the various members of this class of compounds, setting the stage for disparate outcomes later in life.
Pinkas
Adi
A
The Ross Laboratory for Studies in Neural Birth Defects, Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, The Hebrew University, Hadassah Medical School, Box 12272, 91120 Jerusalem, Israel.
Slotkin
Theodore A
TA
Brick-Turin
Yael
Y
Van der Zee
Eddy A
EA
Yanai
Joseph
J
D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D002645:Chickens; D003072:Cognition Disorders / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D007173:Imprinting, Psychological / Q000187:drug effects / Q000502:physiology; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000201:enzymology* / Q000503:physiopathology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D013687:Telencephalon / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D013723:Teratogens / Q000633:toxicity*; D013995:Time
D017738:Alkanesulfonic Acids; D002210:Caprylates; D005466:Fluorocarbons; D007527:Isoenzymes; D013723:Teratogens; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; D011493:Protein Kinase C