Ichiko Nishijima

Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition

BACKGROUND Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. METHODS Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. RESULTS Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. CONCLUSIONS The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits.

Validation of multiple single nucleotide variation calls by additional exome analysis with a semiconductor sequencer to supplement data of whole-genome sequencing of a human population

BackgroundValidation of single nucleotide variations in whole-genome sequencing is critical for studying disease-related variations in large populations. A combination of different types of next-generation sequencers for analyzing individual genomes may be an efficient means of validating multiple single nucleotide variations calls simultaneously.ResultsHere, we analyzed 12 independent Japanese genomes using two next-generation sequencing platforms: the Illumina HiSeq 2500 platform for whole-genome sequencing (average depth 32.4×), and the Ion Proton semiconductor sequencer for whole exome sequencing (average depth 109×). Single nucleotide polymorphism (SNP) calls based on the Illumina Human Omni 2.5-8 SNP chip data were used as the reference. We compared the variant calls for the 12 samples, and found that the concordance between the two next-generation sequencing platforms varied between 83% and 97%.ConclusionsOur results show the versatility and usefulness of the combination of exome sequencing with whole-genome sequencing in studies of human population genetics and demonstrate that combining data from multiple sequencing platforms is an efficient approach to validate and supplement SNP calls.

Secretin is not necessary for exocrine pancreatic development and growth in mice.

Adaptive exocrine pancreatic growth is mediated primarily by dietary protein and the gastrointestinal hormone cholecystokinin (CCK). Feeding trypsin inhibitors such as camostat (FOY-305) is known to induce CCK release and stimulate pancreatic growth. However, camostat has also been reported to stimulate secretin release and, because secretin often potentiates the action of CCK, it could participate in the growth response. Our aim was to test the role of secretin in pancreatic development and adaptive growth through the use of C57BL/6 mice with genetic deletion of secretin or secretin receptor. The lack of secretin in the intestine or the secretin receptor in the pancreas was confirmed by RT-PCR. Other related components, such as vasoactive intestinal polypeptide (VIP) receptors (VPAC(1) and VPAC(2)), were not affected. Secretin increased cAMP levels in acini from wild-type (WT) mice but had no effect on acini from secretin receptor-deleted mice, whereas VIP and forskolin still induced a normal response. Secretin in vivo failed to induce fluid secretion in receptor-deficient mice. The pancreas of secretin or secretin receptor-deficient mice was of normal size and histology, indicating that secretin is not necessary for normal pancreatic differentiation or maintenance. When WT mice were fed 0.1% camostat in powdered chow, the pancreas doubled in size in 1 wk, accompanied by parallel increases in protein and DNA. Camostat-fed littermate secretin and secretin receptor-deficient mice had similar pancreatic mass to WT mice. These results indicate that secretin is not required for normal pancreatic development or adaptive growth mediated by CCK.

Prevalence and determinants of inadequate use of folic acid supplementation in Japanese pregnant women: the Japan Environment and Children’s Study (JECS)

Abstract Objective: The aim of the study was to clarify the prevalence and determinants of inadequate use of folic acid supplementation in pregnant Japanese women. Methods: This study was part of the Japan Environment and Children’s Study, a nationwide and government-funded birth cohort study. We collected information on the use of folic acid supplementation before and during pregnancy and characteristics of participants using self-administered questionnaire. Results: Among 9849 women who completed the data collection for this study, the prevalence of inadequate users was 92.6% of the total population and varied from 84.5% to 96.2% among regions. On the basis of multivariate logistic regression analysis, younger age, not married, lower family income, multipara, natural conception and no history of spontaneous abortion were found to be determinants for inadequate users of folic acid supplementation. Conclusion: Most Japanese pregnant women show inadequate folic acid supplementation use. Japanese women of child-bearing age need to be specifically informed about the need for periconceptional intake of folic acid to prevent neural tube defects.

Drug Use before and during Pregnancy in Japan: The Japan Environment and Children’s Study

Purpose: To elucidate drug use before and during pregnancy in Japan. Methods: The Japan Environment and Children’s Study (JECS) is an ongoing nationwide birth cohort study. We analyzed data from JECS involving cases where drugs were used for 12 months before pregnancy was diagnosed, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy. Results: We analyzed data from 97,464 pregnant women. The percentages of pregnant women who had taken one or more drugs and supplements before diagnosis of pregnancy, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy, were 78.4%, 57.1%, and 68.8% respectively. Excluding iron supplements, folic acid, and other vitamins and minerals, the percentages of women taking supplements were 75.3%, 36.0%, and 51.7% at each respective time point. The following drugs and supplements were frequently used for 12 months before pregnancy diagnosis: Commercially available antipyretics, analgesics, and/or medicine for treating common cold (34.7%), antipyretics, analgesics, and/or medicine for treating common colds, which were prescribed in hospitals (29.8%), antimicrobial drugs (14.0%), and anti-allergy drugs (12.5%). The following drugs and supplements were frequently used from the time of pregnancy diagnosis until week 12 of pregnancy, and after week 12 of pregnancy: folic acid (28.9% and 26.2%), antipyretics, analgesics and/or medicines for treating common cold, that were prescribed in hospitals (7.8% and 13.3%), Chinese herbal medicines (6.0% and 9.4%, and uterine relaxants (5.1% and 15.2%). Conclusions: The analysis of a nationwide cohort study showed that a high percentage of Japanese pregnant women were taking medicinal drugs. Further research is required to elucidate the relationship between drug use during pregnancy and birth defects in Japan.

Incidence of Domestic Violence Against Pregnant Females After the Great East Japan Earthquake in Miyagi Prefecture: The Japan Environment and Children’s Study

OBJECTIVE This study aimed to clarify the correlation between the 2011 Great East Japan Earthquake and domestic violence (DV) against pregnant females after the disaster in Miyagi Prefecture, an area damaged by the earthquake and tsunami. METHODS We analyzed 7600 pregnant females from June to December 2011. The incidence of physical and mental DV and the proportions in the inland, north coastal, and south coastal areas of Miyagi Prefecture and nationwide were calculated, and a chi-square test was conducted for comparison. The risk factors for DV were estimated with multivariate logistic regression analyses on a prefecture-wide basis. RESULTS The incidence levels for physical DV were found to be 5.9% in the north coastal area, which was significantly higher than in the inland area (1.3%, P=0.0007) and nationwide (1.5%, P<0.0001). There were no significant differences in the incidence of mental DV between the 3 areas in Miyagi Prefecture (inland 15.2%, north coast 15.7%, and south coast 18.8%) or nationwide (13.8%). Experiencing disease or injury in someone close and changes in the family structure were significantly associated with mental DV in Miyagi Prefecture. CONCLUSION Continuous monitoring and support for pregnant females may be necessary to address this issue in disaster-affected areas. (Disaster Med Public Health Preparedness. 2017;11:216-226).

Selective serotonin reuptake inhibitors and risk of major congenital anomalies for pregnancies in Japan. A nationwide birth cohort study of the Japan Environment and Children's Study.

We analyzed data from the Japan Environment and Childrens Study (JECS), on the association between selective serotonin reuptake inhibitors (SSRI) use during pregnancy and the risk of developing of major congenital anomalies in Japan. JECS is an ongoing nationwide birth cohort study. The study includes 95 994 single pregnant women and their offspring. Among them, 172 used any SSRI up to the 12th gestational week. Crude analyses show a significantly increased incidence of upper limb, abdominal, and urogenital abnormalities. In particular, the incidence of microcephaly, hydrencephalus, esophageal atresia, small intestinal atresia, and achondroplasia was significantly higher with than without exposure to these substances. On multivariate analyses, urogenital abnormality was significant (odds ratio 3.227; 95% confidence interval: 1.460–7.134). This Japanese nationwide birth cohort survey clarified that the use of any SSRI until the 12th gestational week was associated with urogenital abnormality in children. The survey for association with minor classification abnormality needs further examination in Japan.

Secretin receptor involvement in prion‐infected cells and animals

The cellular mechanisms behind prion biosynthesis and metabolism remain unclear. Here we show that secretin signaling via the secretin receptor regulates abnormal prion protein formation in prion‐infected cells. Animal studies demonstrate that secretin receptor deficiency slightly, but significantly, prolongs incubation time in female but not male mice. This gender‐specificity is consistent with our finding that prion‐infected cells are derived from females. Therefore, our results provide initial insights into the reasons why age of disease onset in certain prion diseases is reported to occur slightly earlier in females than males.

Update on the prevalence and determinants of folic acid use in Japan evaluated with 91,538 pregnant women: the Japan Environment and Children’s Study

Abstract Objective: To provide the latest and most promising evidence on the prevalence and determinants for folic acid supplementation in pregnant women in Japan, including differences in prevalence between interview years and determinants across regions. Materials and methods: The study participants were enrolled from 15 regional centers across Japan between January 2011 and March 2014. Information on the use of folic acid supplementation before and during pregnancy and the characteristics of the participants were collected using questionnaires, medical chart reviews, and interviews by research coordinators. Results: Data for 91,538 women who provided sufficient data on folic acid supplementation were analyzed. The prevalence of adequate users was 8.0%, which, although low, tended to improve over the 4-year recruitment period. Various kinds of sociodemographic factors, lifestyle habits, and obstetrical and medication use history were significant and independent determinants for folic acid use. Associations between adequate preconception folic acid use and its major determinants tended to be similar across regions. Conclusions: Although the prevalence of adequate folic acid use was low, it increased from 2011 to 2014. Reproductive-aged women who have determinants for inadequate folic acid use should be informed about the need for preconception folic acid supplementation to help prevent neural tube defects.

Pregnant Women's Awareness of Social Capital in the Great East Japan Earthquake-Affected Areas of Miyagi Prefecture: The Japan Environment and Children's Study.

OBJECTIVE We aimed to clarify the correlation between the 2011 Great East Japan Earthquake and pregnant womens awareness of social capital 3 to 9 months after the tsunami disaster. METHODS We analyzed data on responses to a questionnaire by 7451 pregnant women in their second to third trimesters. The proportions of social capital-related items were calculated in the north and south coastal areas of Miyagi Prefecture and were compared with national samples. The factors associated with social capital were estimated by use of multivariate logistic regression analyses. RESULTS The proportion of women feeling that they had helpful neighbors was higher (69.0% vs 56.7%, P=0.0005), the proportion of women regarding their communities as safe and secure was lower (51.7% vs 62.4%, P=0.002), and the proportion of women feeling that most people were trustworthy was lower (23.7% vs 32.9%, P=0.006) in the north coastal area than nationwide. Such differences were not observed in the less severely affected south coastal area. Age of 35 years or older, extended family, college or university graduation, and being multiparous were associated with the feeling of having helpful neighbors. CONCLUSION The current status of pregnant womens awareness of social capital in disaster-affected areas was revealed. Continuous monitoring and support may be necessary to address this issue.(Disaster Med Public Health Preparedness. 2017;11:355-364).