Effects of perinatal coexposure to methylmercury and polychlorinated biphenyls on neurobehavioral development in mice.
Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmental pollutants that cause neurobehavioral deficits in humans. Because exposures to MeHg and PCBs occur through fish consumption, it is necessary to clarify the effects of the interaction of the two pollutants. Therefore, we investigated the effects of perinatal exposure to MeHg and PCBs on the neurobehavioral development in mice. Female mice (C57BL/6Cr) were divided into four groups according to the type of exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, and (4) MeHg + PCBs. The MeHg-exposed groups were fed with a diet containing 5 ppm MeHg (as Hg), from 4 weeks before mating, throughout pregnancy, and lactation. The PCB-exposed groups were given a commercial mixture of PCBs, Aroclor 1,254, at 18 mg/kg body weight in corn oil by gavage every 3 days from day 5 after breeding and continued until postnatal day (PND) 20. Before weaning, an assessment of eye opening showed the interactive effects between MeHg and PCBs on PND 12: The coexposure group showed a similar response to the control group, whereas the MeHg- and PCB-exposed groups showed a high response than the former two groups. We also observed delay in development of grasp reflex by MeHg exposure on PNDs 12 and 14. When the offspring mice were 8 weeks old, the group exposed to PCBs alone showed increases in the frequencies of excrement defecation and urine traces in an open-field test. Analysis of the latency revealed the antagonistic interaction between the MeHg and PCBs: The latency increased by either MeHg or PCB exposure was decreased by coexposure. Treatment with MeHg decreased the distance walked by the mice, and MeHg interacted with PCBs. Moris' water maze test showed that the MeHg-treated mice took a long time to reach the submerged platform; however, this MeHg exposure showed no interaction with PCB exposure. The spontaneous locomotion activity of the mice was not affected by the chemical exposure at 9 weeks of age. These behavioral changes were not accompanied by any histopathological changes at the levels of the frontal cortex-caudoputamen, hippocampus-amygdala, brainstem and cerebellum. These results show that perinatal coexposure to MeHg and PCBs produces no additive or synergistic effects. This phenomenon needs to be further investigated.
Sugawara
Norio
N
Environmental Health Sciences, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Ohba
Takashi
T
Nakai
Kunihiko
K
Kakita
Akiyoshi
A
Nakamura
Tomoyuki
T
Suzuki
Keita
K
Kameo
Satomi
S
Shimada
Miyuki
M
Kurokawa
Naoyuki
N
Satoh
Chieko
C
Satoh
Hiroshi
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D003216:Conditioning, Operant / Q000187:drug effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004785:Environmental Pollutants / Q000633:toxicity*; D005123:Eye / Q000187:drug effects / Q000254:growth & development; D005260:Female; D007774:Lactation / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D018782:Maze Learning / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D020111:Chlorodiphenyl (54% Chlorine)