Neurobehavioral effects of prenatal exposure to methylmercury and PCBs, and seafood intake: neonatal behavioral assessment scale results of Tohoku study of child development.

As factors affecting neonatal neurodevelopment, methylmercury, polychlorinated biphenyls (PCBs), and maternal seafood intake reflecting n-3 polyunsaturated fatty acids (PUFAs) are believed to have adverse or beneficial effects, but there are a few reports addressing such factors simultaneously. We carried out a birth cohort study to clarify the effects of these three factors on the Neonatal Behavioral Assessment Scale (NBAS), administered 3 days after birth. In a total of 498 mother-neonate pairs, the total mercury level (median, 1.96microg/g) in maternal hair at parturition and the summation operatorPCB level (45.5ng/g-lipid) in cord blood were analyzed, and maternal seafood intake was estimated using a semi-quantitative food frequency questionnaire. A negative relationship between the hair mercury level and the motor cluster of NBAS was observed, even after adjusting for PCBs, maternal seafood intake, and possible confounders such as maternal age, birth weight, and parity. The summation operatorPCB level was negatively correlated with the motor cluster, but this association was attenuated after adjusting for mercury and the confounders. There was seen to be a positive association between maternal seafood intake and the motor cluster when considering the effects of mercury and PCBs. In conclusion, our data suggest that prenatal exposure to methylmercury adversely affects neonatal neurobehavioral function; in contrast, maternal seafood intake appears to be beneficial. The neurobehavioral effect of prenatal exposure to PCBs remains unclear in our study. Further research is necessary to elucidate interactive effects of methylmercury, PCBs, and n-3 PUFAs, originating from fish, on child neurodevelopment.

Lipopolysaccharide activates the kallikrein-kinin system in mouse choroid plexus cell line ECPC4.

Regulation of the kallikrein-kinin system in cerebral inflammation is still unclear. Here, we used reverse-transcription polymerase chain reaction (RT-PCR) techniques to show that lipopolysaccharide (LPS) activates the kallikrein-kinin system by enhancing liberation of bradykinin (BK), and alters mRNA levels of kallikrein-kinin system components, including high molecular weight (H-) and low molecular weight (L-) kininogens, in ECPC4 cells, a cell line of mouse choroid plexus epithelium. LPS treatment increased liberation of immunoreactive bradykinin in the supernatant of ECPC4 cells, and addition of LPS (500 ng/ml) to cultures resulted in elevation of H- and L-kininogen mRNA levels in ECPC4 cells within 24-48 h. Furthermore, LPS treatment elevated bradykinin type 2 and type 1 receptor mRNA levels within 4h, but did not change tissue kallikrein or plasma kallikrein mRNA levels. On the other hand, expression of pro-inflammatory mediators interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and cyclooxygenase-2 mRNA increased within 4-8h after addition of LPS to ECPC4 cells. The addition of IL-1beta and TNF-alpha to investigate the major mediator for kininogen expression in ECPC4 cells remarkably induced expression of H- and L-kininogen mRNAs in ECPC4 cells. These results suggest that LPS activates the kallikrein-kinin system in the choroid plexus via autocrine induction of IL-1beta and TNF-alpha.

Permanent waving does not change mercury concentration in the proximal segment of hair close to scalp.

Mercury in hair is a generally accepted biomarker of methylmercury exposure, and permanent waving has been reported to affect the mercury concentration in hair. We conducted an experimental-field study to examine the changes in the mercury concentration in hair induced by treatments such as permanent waving, straightening and coloring. Hair samples were collected from 19 female subjects enrolled before and after hair treatment by a beautician during each visit to a beauty saloon. A total of 38 pair samples were cut in 1-cm segments from the proximal end up to 10 cm, and then as 2-cm segments up to the distal end thereafter. Each segment was analyzed for total mercury concentration by cold-vapor atomic absorption spectrometry. Permanent waving decreased mercury concentration for most of the segments except for the proximal two segments and the 8-9 cm segment from the proximal end. Nevertheless the average mercury concentration of 3-cm segments from the proximal end showed no significant decrease by permanent waving. Since females usually have hair longer than 3 cm, hair samples subjected to permanent waving may give lower mercury exposure estimates when the full-length hair strands are analyzed. However, analyzing the proximal 3-cm segment of hair samples does not give lower mercury exposure estimates. Assuming that hair samples are collected from puerperal women around the time of delivery, the 3-cm segments represent fetal exposure to methylmercury during the third trimester when fetuses are most vulnerable to methylmercury exposure. Therefore, mercury concentrations in the proximal segment of maternal hair collected in the right time can be a good biomarker of fetal methylmercury exposure.

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.

Association of maternal smoking during pregnancy and infant neurobehavioral status.

The association of maternal smoking during pregnancy with neurobehavioral status was examined in 344 Japanese infants. Based on a questionnaire, their mothers were classified into three groups, Nonsmokers, Exsmokers, and Smokers. The Neonatal Behavioral Assessment Scale was administered three days after birth. Among the three groups, on the seven clusters and their 28 behavioral subscales there were no significant differences. The infants of Smokers had lower scores than those of Exsmokers and Nonsmokers on two behavioral items, general tone and peak of excitement. General tone remained significant after adjustment for covariates.

Developmental and neurobehavioral effects of perinatal exposure to polychlorinated biphenyls in mice.

Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning.