Cui Chun, Sakata-Haga Hiromi, Ohta Ken-ichi, Nishida Manami, Yashiki Mikio, Sawada Kazuhiko, Fukui Yoshihiro
Department of Anatomy and Developmental Neurobiology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Congenit Anom (Kyoto). 2006 Dec;46(4):180-7. doi: 10.1111/j.1741-4520.2006.00126.x.
When pregnant women abuse methamphetamine, the foremost concern is the potential adverse effect of this substance on fetal development. Clinical studies in humans have found that exposure to methamphetamine during brain development can cause neurobehavioral abnormalities, such as aggressive behavior, learning problems, and poor social adaptation. In the present study, we examined the effects of prenatal methamphetamine exposure on brain development in rats. The first group of pregnant rats was administered methamphetamine at a dose of 5 mg/kg/day during gestational day (GD 10 to GD 20 [MA]. The second group of pregnant rats was injected with saline vehicle only [SAL]. On GD 21 their fetuses were removed and fetal brains were observed. We found various types of morphological damage in MA fetal brains, including microgyria, ectopia, and hemorrhage. In some cases, abnormal distribution of the leptomeninx, such as breach or accumulation, was observed in addition to these histological abnormalities. Therefore, we examined the expression of laminin, which is an important component of the pia mater, in the fetal brains. However, Western blot analysis revealed that there was no difference in expression amount of laminin in whole fetal brain between the MA and SAL groups. We concluded that methamphetamine use during pregnancy can cause histological brain alterations in fetuses. Morphological alterations of brain seen in the present study and previous human studies following prenatal exposure to methamphetamine might be related to the neurobehavioral abnormalities seen in patients who had been exposed to methamphetamine in utero.
孕妇滥用甲基苯丙胺时,最主要的担忧是该物质对胎儿发育的潜在不良影响。人体临床研究发现,在大脑发育过程中接触甲基苯丙胺会导致神经行为异常,如攻击性行为、学习问题和社会适应能力差。在本研究中,我们检测了产前接触甲基苯丙胺对大鼠大脑发育的影响。第一组怀孕大鼠在妊娠第10天至第20天(GD 10至GD 20)期间以5 mg/kg/天的剂量给予甲基苯丙胺[MA组]。第二组怀孕大鼠仅注射生理盐水载体[SAL组]。在妊娠第21天取出它们的胎儿并观察胎儿大脑。我们在MA组胎儿大脑中发现了各种类型的形态学损伤,包括小脑回、异位和出血。在某些情况下,除了这些组织学异常外,还观察到软脑膜的异常分布,如破裂或积聚。因此,我们检测了胎儿大脑中作为软脑膜重要组成部分的层粘连蛋白的表达。然而,蛋白质印迹分析显示,MA组和SAL组之间全胎儿大脑中层粘连蛋白的表达量没有差异。我们得出结论,孕期使用甲基苯丙胺可导致胎儿大脑组织学改变。本研究以及先前人类研究中产前接触甲基苯丙胺后所见的大脑形态学改变可能与子宫内接触过甲基苯丙胺的患者中所见的神经行为异常有关。