POLYCHLORINATED BIPHENYLS PCB 153 AND PCB 126 IMPAIR THE GLUTAMATE-NITRIC OXIDE-cGMP PATHWAY IN CEREBELLAR NEURONS IN CULTURE BY DIFFERENT MECHANISMS

摘要

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 glu-NO-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 PCB153 or 126 reproduces the impairment in the function of the glu-NO-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 PCB126 and PCB153. Both PCB153 and PCB126 increase basal levels of cGMP by different mechanisms. PCB126 increases the amount of soluble guanylate cyclase while PCB153 does not. PCB153 reduces the amount of calmodulin while PCB126 does not. Also both PCBs impair the function of the glu-NO-cGMP pathway by different mechanisms; PCB153 impairs NO-induced activation of sGC and increase in cGMP while PCB126 does not. PCB126 reduces NMDA-induced increase in calcium while PCB153 does not.