Developmental exposure to polychlorinated biphenyls 52, 138 or 180 affects differentially learning or motor coordination in adult rats. Mechanisms involved.
Exposure to polychlorinated biphenyls (PCBs) during pregnancy and lactation leads to cognitive impairment and motor disorders in children by mechanisms which remain unknown. It also remains unclear whether different non-dioxin-like PCBs have similar or different mechanisms of neurotoxicity. The main aims of this work were: (1) to assess whether developmental exposure to non-dioxin-like-PCBs 52, 138 or 180 affect cognitive function or motor coordination in 3-4 months-old rats; (2) to shed light on the underlying mechanisms. Female rats were treated with PCBs (1 mg/kg day) in food from gestational-day 7 to postnatal-day 21. The ability to learn a Y maze conditional discrimination task was reduced in rats exposed to PCBs 138 or 180, but not in rats exposed to PCB52. The function of the glutamate-nitric oxide-cGMP pathway (NMDA-induced increase in extracellular cGMP) in cerebellum in vivo was reduced by 33-59% in rats exposed to PCBs 138 or 180, but not by PCB52. The amount of NR1 subunit of NMDA receptors was reduced by 41-49% in rats exposed to PCBs 138 or 180, but not by PCB 52. PCB52 but not 138 or 180 increases extracellular GABA in cerebellum and impairs motor coordination. The effects were similar in males and females. Developmental exposure to different non-dioxin-like PCBs induces different behavioural alterations by different mechanisms. PCB52 impairs motor coordination but not learning while PCB138 or 180 impair learning but not motor coordination. These data are consistent with the following possible mechanisms: (1) developmental exposure to PCBs 138 or 180 reduces the amount of NMDA receptors in cerebellum, which would contribute to reduced function of the glutamate-NO-cGMP pathway, which, in turn, would be a main contributor to the impairment of the ability to learn the Y maze task. (2) Developmental exposure to PCB52 increases extracellular GABA in cerebellum, which would contribute to motor coordination impairment.
Boix
J
J
Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Avda Autopista del Saler, 16, 46012 Valencia, Spain.
Cauli
O
O
Felipo
V
V
D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004192:Discrimination, Psychological / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007858:Learning / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D018782:Maze Learning / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000523:psychology*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012737:Sex Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D004785:Environmental Pollutants; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; C009407:2,5,2',5'-tetrachlorobiphenyl; D018698:Glutamic Acid; C410127:PCB 180; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; C029790:2,2',3',4,4',5-hexachlorobiphenyl; D011078:Polychlorinated Biphenyls; D006152:Cyclic GMP