The long-term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy.
The long-term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy.
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妊娠期丙戊酸暴露大鼠子代海马神经发生和行为改变的远期预后。
DOI：
10.1002/npr2.12181
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发表时间：
2021-06
影响因子：
2.5
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Ito M;Kinjo T;Seki T;Horie J;Suzuki T
在患有癫痫的孕妇中，必须平衡产妇安全和抗惊厥药物的潜在致畸性。近年来，越来越多的证据表明丙戊酸（VPA）可导致出生后先天性畸形和认知功能损害。然而，认知功能障碍在长期预后中的潜在机制仍不清楚。妊娠Wistar大鼠从胚胎第12.5天至出生，每天腹腔注射VPA （200 mg/kg/天）。在出生后第149天，大鼠接受溴脱氧尿苷（BrdU）注射。在PD 150，大鼠进行了开放场（OF）、升高正迷宫（EPM）和Y迷宫测试。行为学测试结束后，进行灌注固定，解剖脑组织进行免疫组化。与对照组相比，经VPA处理的幼鼠齿状回中BrdU阳性细胞的数量显著减少。然而，在200只VPA处理过的水坝中，在PD 150的后代中，根据of测试的结果，没有发现多动症的显著差异。此外，在EPM测试中未见显著差异。经VPA处理的幼鼠的行为异常与PD - 150处理的成年鼠的行为异常无显著差异。然而，与对照组相比，VPA处理的大鼠BrdU阳性细胞数量减少了一半。研究结果表明，行为异常似乎随着他们的成长而改善，即使中枢神经系统可能仍然存在一些结构异常。妊娠Wistar大鼠从胚胎第12.5天至出生，每天腹腔注射VPA （200 mg/kg/d）。在出生后第149天，大鼠接受溴脱氧尿苷（BrdU）注射。与对照组相比，经VPA处理的幼鼠齿状回中BrdU阳性细胞的数量显著减少。
In pregnant women with epilepsy, it is essential to balance maternal safety and the potential teratogenicity of anticonvulsants. Recently, growing evidence has indicated that valproic acid (VPA) can produce postnatal congenital malformations and impair cognitive function. However, the mechanisms underlying cognitive dysfunction in long‐term prognoses remain unclear. Pregnant Wistar rats received daily intraperitoneal injections of VPA (200 mg/kg/day) from embryonic day 12.5 until birth. On postnatal day (PD) 149, the rats received an injection of bromodeoxyuridine (BrdU). On PD 150, the rats were subjected to the open field (OF), elevated plus‐maze (EPM), and Y‐maze tests. After behavioral testing, perfusion fixation was performed and the brain was dissected for immunohistochemistry. A significant marked decrease was seen in the number of BrdU‐positive cells in the dentate gyrus of offspring of VPA‐treated dams compared to those of control. However, no significant differences in hyperactivity were found based on the results of the OF test among the offspring on PD 150 of 200 VPA‐treated dams. In addition, no significant differences were seen in the EPM test. The behavioral abnormality observed in young offspring of VPA‐treated dams was not significantly different from that of controls in adult offspring on PD 150. However, compared with controls, the number of BrdU‐positive cells in VPA‐treated rats was halved. The findings suggest that the behavioral abnormality seems to improve as they grow, even if some structural abnormalities may remain in the central nervous system. Pregnant Wistar rats received daily intraperitoneal injections of VPA (200 mg/kg/d) from embryonic day 12.5 until birth. On postnatal day (PD) 149, the rats received an injection of bromodeoxyuridine (BrdU). A significant marked decrease was seen in the number of BrdU‐positive cells in the dentate gyrus of offspring of VPA‐treated dams compared to those of control.
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7.6
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Przewlocki, R