title: Gender differential effects of developmental exposure to methyl-mercury, polychlorinated biphenyls 126 or 153, or its combinations on motor activity and coordination.
abstract: Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are persistent organic pollutants accumulating in the food chain. Pre- and neonatal exposure to these neurotoxicants may affect brain development and lead to long-lasting alterations in cerebral function, which can result in motor alterations in youth and/or adulthood. Some neurotoxicants induce gender specific effects. The aims of the present work were to: (1) assess the effects of developmental exposure to MeHg, PCB 153 or PCB 126 on spontaneous locomotor and vertical activity and motor coordination when the rats are 2-month old; (2) assess whether perinatal exposure to combinations of MeHg with PCB153 or PCB126 alter the effects of the individual neurotoxicants; (3) follow the progression of motor alterations when the rats are 3-, 5- and 7-month old; (4) assess if the effects are similar or different in males and females. Pregnant rats were treated with MeHg (0.5mg/kgday); PCB126 (100ng/kgday) or PCB153 (1mg/kgday) or with combinations of MeHg with each PCB, administered in food from gestational day 7 until weaning at post-natal day 21. PCB 126 impaired motor coordination at 2 months in males but not in females. PCB 153 impaired coordination both in males and females. Combinations of MeHg with PCB153 or PCB126 did not affect motor coordination, indicating that MeHg counteracts the effects of the PBCs. The combination of MeHg and PCB153 induces hypolocomotion at 2 months but hyperactivity at 7 months while the individual compounds did not induce any effect. PCB126 induced gender selective effects, reducing locomotor activity at 2 months in females but not in males. The combination of MeHg and PCB126 behaves as PCB126 alone. All compounds and combinations tested induce gender-selective alterations in vertical activity. The effects on locomotor and vertical activity change with age in the same rats. At 2 months all compounds and combinations reduce vertical activity in females but not in males. At 7 months all treatments induced hyperactivity both in males and females, except MeHg+PCB126. In conclusion, the results show that: (a) many motor alterations induced by most compounds are different in males and females; (b) mixtures of MeHg with PCBs 153 or 126 induce different effects that the individual compounds; (c) different types of motor activity (spontaneous locomotion, vertical activity and motor coordination) are affected differently by the same neurotoxicant or mixture; and (d) the effects on locomotor and specially on vertical activity change with the age of the rat. Most compounds reduce activity at youth (2 months) and induce hyperactivity at adulthood (5-7 months). The change from hypo- to hyperactivity occurs earlier in males.
authors.affiliation: Laboratory of Neurobiology, Centro de Investigación Principe Felipe, Valencia, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Cauli
authors.forename: Blanca
authors.initials: B
authors.lastname: Piedrafita
authors.forename: Marta
authors.initials: M
authors.lastname: Llansola
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
mesh_terms: D000818:Animals; D004338:Drug Combinations; D005260:Female; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
chemical_list: D004338:Drug Combinations; D008767:Methylmercury Compounds; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl