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Nakagami A.,Japan Womens University | Koyama T.,Japan Womens University | Kawasaki K.,Hoshi University | Negishi T.,Aoyama Gakuin University | And 3 more authors.
Developmental Psychobiology | Year: 2011

Polychlorinated biphenyls (PCBs) are endocrine disrupting chemicals that disturb normal development of embryonic brains. In the present study, we evaluated the relationship between maternal plasma PCB concentration and infant behavioral characteristics in mother-infant interactions. We grouped 20 pregnant cynomolgus monkeys (Macaca fascicularis) into higher and lower PCB exposure groups; monkeys in the higher PCB group had PCB concentrations above 15 pg/g, which is representative of natural exposure levels. Maternal PCB concentration correlated negatively with infant behaviors (approach, look, proximity, locomotion) at the age of 6 months (p < .05), when an increase in these behaviors should normally occur. These results suggest that maternal PCB exposure may affect the development of infant social behavior in cynomolgus monkeys. Furthermore, this study provides primate evidence to support observations of associations between behavioral and learning disabilities and prenatal exposure to PCBs in humans. © 2010 Wiley Periodicals, Inc.

Ise R.,Drug Safety Research Laboratories | Kondo S.,Toray Industries Inc | Kato H.,Drug Safety Research Laboratories | Imai N.,Drug Safety Research Laboratories | And 4 more authors.
Drug Metabolism and Pharmacokinetics | Year: 2011

Preclinical data of fetal, infant, and juvenile animals are important for the prediction of drug toxicity in fetuses and children. However, expression of drug-metabolizing enzymes, including cytochromes P450 (CYPs), have not been fully investigated in fetal, infant, or juvenile liver of the cynomolgus macaque, an animal species important for preclinical studies. In this study, hepatic expression of 20 cynomolgus macaque CYPs (mfCYPs) in the CYP14 subfamilies that are relevant to drug metabolism was measured in fetuses, infants, and juveniles using DNA microarrays. Expression of most mfCYPs, including those moderately or abundantly expressed in postnatal livers such as mfCYP2A23, mfCYP2A24, mfCYP2B6, mfCYP2C9, mfCYP2C19, mfCYP2C76, mfCYP2D17, mfCYP2E1 mfCYP3A4, and mfCYP3A5, was much less abundant in fetal livers, but increased substantially after birth. In contrast, expression of mfCYP2C8 in fetal livers was not substantially different from postnatal livers. Since human CYP3A7 is expressed more abundantly in fetal livers than in adult livers, mfCYP3A7, an ortholog of human CYP3A7, was analyzed by quantitative polymerase chain reaction. Expression of mfCYP3A7 in fetal livers was much lower than that in postnatal livers, and greatly increased after birth, unlike the expression of human CYP3A7. These results indicate that expression of most mfCYPs examined was low in fetal livers, but increased greatly in postnatal livers, with a few exceptions such as mfCYP2C8. © 2011 by the Japanese Society for the Study of Xenobiotics (JSSX).

Sawada K.,Tsukuba International University | Fukunishi K.,Shin Nippon Biomedical Laboratories | Kashima M.,Shin Nippon Biomedical Laboratories | Imai N.,Shin Nippon Biomedical Laboratories | And 5 more authors.
Congenital Anomalies | Year: 2012

Cynomolgus monkey (Macaca fascicularis) is a popular laboratory primate belonging to Old World monkeys, which are the group most closely related to humans except for the apes. This paper summarizes a series of our studies regarding the development of cerebral sulci and gyri in this primate, and the stated possibility of evaluation of the sulcal development for assessing the developmental toxicity testing. The cerebrum of cynomolgus monkeys experienced a regular sequence of emergence of sulci and gyri on gross observation while such timetables corresponded to those obtained by magnetic resonance imaging (MRI) with a lag time of 10-30 days. When the timetables for the emergence of anatomically identical primary sulci and gyri were compared between cynomolgus monkeys and humans, their chronological sequences were comparable, while some sulci and gyri located on the phylogenetically newer cortical region in humans emerged earlier in monkeys. The present paper further indicates brief procedures for evaluating cerebral abnormalities and/or maturity using brain specimens without MRI measurements. The primary sulcal lengths measured by the 'cotton thread' method were a brief index of the degree of regional gyrification. As the development of a calcarine sulcus was closely correlated with morphological maturation of the lateral ventricle, which changed drastically during embryonic days (EDs) 90-100, the cerebral maturity on ED 100 could be evaluated by the infolding of that sulcus. Thus, the present paper provides gross anatomical and MRI references and brief procedures for investigating the normality of the development of cerebral sulci and gyri of laboratory primates, cynomolgus monkeys. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

Sawada K.,Tsukuba International University | Fukunishi K.,Shin Nippon Biomedical Laboratories | Kashima M.,Shin Nippon Biomedical Laboratories | Saito S.,Japan National Institute of Radiological Sciences | And 4 more authors.
Anatomical Record | Year: 2012

Our article summarizes a series of studies about fetal gyrification and its relation to cerebral growth in cynomolgus monkeys. Based on the cerebral growth (i.e., brain weight, cerebral volume, and frontooccipital length of the cerebral hemisphere) and the developmental pattern of gyrification in each sulcus of cynomolgus monkeys, we divided the gyrification process into four stages: Stage 1. Demarcation of cerebral lobes and limbic gyri; Stage 2. Demarcation of neocortical gyri; Stage 3. Emergence of secondary and tertiary sulci; and Stage 4. Growth of sulcal length and depth. Each stage of those gyrification processes was influenced by different developmental events, such as the emergence of corticocortical long-associative fiber tracts, cortical maturations, and subcortical white-matter development. This is the first report to systematically propose gyrification processes closely related to the order of phyologenetical development of the cerebral cortex in primates. © 2012 Wiley Periodicals, Inc.

Imai N.,Tokushima University | Imai N.,Shin Nippon Biomedical Laboratories | Sawada K.,Tsukuba International University | Fukunishi K.,Shin Nippon Biomedical Laboratories | And 2 more authors.
Congenital Anomalies | Year: 2011

The present study aimed to quantitatively clarify the gross anatomical asymmetry and sexual dimorphism of the cerebral hemispheres of cynomolgus monkeys. While the fronto-occipital length of the right and left cerebral hemispheres was not different between sexes, a statistically significant rightward asymmetry was detected in the cerebral width at the perisylvian region in females, but not in males (narrower width of the left side in the females). An asymmetry quotient of the sulcal lengths revealed a rightward asymmetry in the inferior occipital sulcus and a leftward asymmetry in the central and intraparietal sulci in both sexes. However, the laterality of the lengths of other sulci was different for males and females. The arcuate sulcus was directed rightward in males but there was no rightward bias in females. Interestingly, the principle sulcus and lateral fissure were left-lateralized in the males, but right-lateralized in the females. The results suggest that lateralization patterns are regionally and sexually different in the cerebrum of cynomolgus monkeys. The present results provide a reference for quantitatively evaluating the normality of the cerebral cortical morphology in cynomolgus monkeys. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

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