Histone modification in a rat fetal brain an neuronal network formation in a rat neonate after prenatal valproic acid treatment.

产前丙戊酸治疗后大鼠胎儿大脑中的组蛋白修饰和新生儿神经元网络的形成。

• 批准号: 21591421
• 负责人: KUWAGATA Makiko
• 金额: $ 2.75万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591421/
• 关键词: 胎児医学; 脳発達障害; バルプロ酸; 胎児脳ヒストン修飾; 新生児神経回路; 胎児脳ピストン回路; 新生児期神経回路

Clinical reports revealed that VPA exposure during early pregnancy increases the risk of a child having an autistic disorder. In this study, focusing on VPA pharmacological action, inhibition of histone deacetylase, the relationship between histone modification and morphological changes in the rat fetal brain after VPA treatment was examined. Disruption of neuronal migration in the cortex was detected in SD, F344 as well as Wistar Kyoto(WK) rat fetus at the gestational day(GD) 16 after VPA treatment at GD11. However, abnormal neural running tract in the midbrain was observed in SD rat fetal brain, but not in F344 or WK rat fetal brain, indicating that "some" morphological changes in the fetal brain are partly due to genetic factors. In the functional observation of neonates on postnatal day 11, an abnormal brain function, such as an increase in fear response, was identified on analyzing the distribution of c-Fos immunoreactive cells after maternal derivation in neonate treated prenatally with VPA. The study could not go to schedule in order to different sensitivity for VPA among rat strains. Therefore, effects of histone modification by VPA on morphological changes in a rat fetal brain have not revealed in this study period.

临床报告显示，怀孕早期接触VPA会增加儿童患自闭症障碍的风险。本研究从VPA的药理作用、对组蛋白脱乙酰酶的抑制作用等方面，探讨了VPA处理后大鼠胎脑组织中组蛋白修饰与脑组织形态变化的关系。在SD、F344和Wistar京都(WK)大鼠胚胎中，在GD11进行VPA治疗后的第16天(GD)，检测到皮质神经元迁移的中断。然而，在SD大鼠胎脑中观察到异常的神经运动束，而在F344和WK大鼠胎脑中未观察到，这表明胎脑的“某些”形态变化部分是由遗传因素引起的。在出生后第11天的新生儿功能观察中，通过分析母体衍生后给予VPA治疗的新生儿的c-Fos免疫反应细胞的分布，发现了异常的脑功能，如恐惧反应增加。由于不同品系大鼠对VPA的敏感性不同，本研究未能如期进行。因此，在本研究期间，VPA修饰组蛋白对大鼠胎脑形态变化的影响尚未被揭示。

项目成果

Characteristic behavioral anomalies in rats prenatally exposed to 5-bromo-2'-deoxyuridine

产前暴露于 5-溴-2-脱氧尿苷的大鼠的特征性行为异常

• 发表时间: 2009
• 期刊: Int J Dev Neurosci
• 影响因子: 1.8
• 作者: Orito K.;Morishima A.;Ogawa T.;Muneoka K.;Kuwagata M.;Takata J.;Mishima K.;Fujiwara M.
• 通讯作者: Fujiwara M.

An Attempt to Cell Recovery Factor in the Cell differentiation culture with the embryonic stem cell test(EST)

胚胎干细胞试验（EST）在细胞分化培养中细胞恢复因子的尝试

• 发表时间: 2009
• 期刊: J. Oral Tissue. Engin
• 作者: Imai K.;Kusakawa S.;Tanoe A.;Kuwagata M.;Senuma M.;Furuya M.;Takashima H.
• 通讯作者: Takashima H.

ラット胎生期ヒ素曝露の胎児脳発達への影響

大鼠产前砷暴露对胎儿脑发育的影响

• 发表时间: 2011
• 作者: 瀬沼美華;古谷真美;高島宏昌;太田亮;小川哲郎;桑形麻樹子
• 通讯作者: 桑形麻樹子

Effects of the genotoxic agent 5-bromo-2'-deoxyuridine with or without pre-pubertal gonadoectomy on brain monoamines an their metabolites in female rats

基因毒性剂 5-溴-2-脱氧尿苷伴或不伴青春期前性腺切除术对雌性大鼠脑单胺及其代谢物的影响

• 发表时间: 2011
• 期刊: Brain Res Bull
• 影响因子: 3.8
• 作者: Kuwagata M;他3名
• 通讯作者: 他3名

Teratogenicity and maternal effects of Lactobacillus brevis KB290 in rats and rabbits.

短乳杆菌 KB290 对大鼠和兔子的致畸性和母体影响。

• 发表时间: 2010
• 期刊: Food Chem Toxicol
• 影响因子: 4.3
• 作者: T.Yakabe;Kuwagata M;他4名
• 通讯作者: 他4名