Polychlorinated biphenyls PCB 153 and PCB 126 impair the glutamate-nitric oxide-cGMP pathway in cerebellar neurons in culture by different mechanisms.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants present in human blood and milk. Exposure to PCBs during pregnancy and lactation leads to cognitive impairment in children. Perinatal exposure to PCB 153 or PCB 126 impairs the glutamate-nitric oxide-cGMP pathway in cerebellum in vivo and learning ability in adult rats. The aims of this work were: (1) to assess whether long-term exposure of primary cultures of cerebellar neurons to PCB 153 or PCB 126 reproduces the impairment in the function of the glutamate-nitric oxide-cGMP pathway found in rat cerebellum in vivo; (2) to provide some insight on the steps of the pathway affected by these PCBs; (3) to assess whether the mechanisms of interference of the pathway are different for PCB 126 and PCB 153. Both PCB 153 and PCB 126 increase basal levels of cGMP by different mechanisms. PCB 126 increases the amount of soluble guanylate cyclase while PCB 153 does not. PCB 153 reduces the amount of calmodulin while PCB 126 does not. Also both PCBs impair the function of the glutamate-nitric oxide-cGMP pathway by different mechanisms, PCB 153 impairs nitric oxide-induced activation of soluble guanylate cyclase and increase in cGMP while PCB 126 does not. PCB 126 reduces NMDA-induced increase in calcium while PCB 153 does not. When PCB 153 and PCB 126 exhibit the same effect, PCB 126 was more potent than PCB 153, as occurs in vivo.
Llansola
Marta
M
Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Avda Autopista del Saler, 16, 46012 Valencia, Spain.
Piedrafita
Blanca
B
Rodrigo
Regina
R
Montoliu
Carmina
C
Felipo
Vicente
V
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018683:Excitatory Amino Acid Agents / Q000633:toxicity; D018698:Glutamic Acid / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D018683:Excitatory Amino Acid Agents; D009498:Neurotoxins; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D011078:Polychlorinated Biphenyls; D006152:Cyclic GMP; D002118:Calcium; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl