Prenatal phencyclidine induces heightened neurodegeneration in rats in some brain regions, especially during 2nd trimester, but possible anti-apoptotic effects in others.
Prenatal phencyclidine induces heightened neurodegeneration in rats in some brain regions, especially during 2nd trimester, but possible anti-apoptotic effects in others.
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产前苯环己哌啶会导致大鼠某些大脑区域的神经变性加剧，尤其是在妊娠第二个月，但在其他区域可能具有抗细胞凋亡作用。
DOI：
10.1034/j.1600-0773.2002.900105.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Ellison,Gaylord
中科院分区：
文献类型：
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作者：
Jebelli,AzadehKokabi;Doan,Ngan;Ellison,Gaylord
在晚期胎儿生命期间，以高剂量给予发育中的大鼠大脑几个小时的苯环利定诱导几个脑区域的凋亡性神经变性。我们试图研究在不同的妊娠期（妊娠中期与妊娠晚期），胎儿长期低水平暴露于苯环利定是否会对几个脑区产生不同的影响，这些脑区显示使用银染色评估的神经变性。妊娠大鼠通过微型泵连续5天接受苯环己哌啶（5.45 mg/天）给药，幼仔出生后立即灌注并进行银染色以检查变性，或使其成熟，然后检测行为缺陷。在新生幼仔中，内嗅皮层和下托中嗜农细胞数量大幅增加;在妊娠中期给予药物时，这种影响更大。然而，在下丘脑腹内侧核，第2和第3孕期苯环己哌啶幼仔有显着较少的退化细胞比对照组。允许成熟的幼仔的旋转棒和旷场表现的行为测试表明，第3个月的苯环己哌啶幼仔的运动协调性和多动性降低，但第2个月的幼仔的变化极小。因此，产前暴露于苯环利定可以有神经退行性或抗凋亡的影响，这取决于大脑区域，并有持续的行为缺陷和细胞损失的药物的最大产前效果的时间之间的差异。
Phencyclidine administered to the developing rat brain at high doses for a few hours during late foetal life induces apoptotic neurodegeneration in several brain regions. We sought to investigate whether prolonged, low level foetal exposure to phencyclidine during different gestational periods (2nd trimester versus 3rd trimester) would have different effects on several brain regions showing neurodegeneration as assessed using silver stains. Pregnant rats were treated with phencyclidine (5.45 mg/day) continuously for 5 days via minipumps, and the pups were either perfused immediately after birth and silver‐stained for degeneration, or allowed to mature and then tested for behavioural deficits. In the newborn pups, there was a substantial increase in the number of agrophilic cells in entorhinal cortex and subiculum; this effect was greater when the drug was given during 2nd trimester. However, in the ventromedial nucleus of the hypothalamus, both the 2nd and 3rd trimester phencyclidine pups had significantly fewer degenerating cells than the controls. Behavioural tests of rotorod and open field performance in the pups allowed to mature indicated decreased motor coordination and hyperactivity in the 3rd trimester phencyclidine pups, but minimal alterations in the 2nd trimester pups. Thus, prenatal exposure to phencyclidine can have either neurodegenerative or antiapototic effects depending upon brain region, and there is a discrepancy between persisting behavioural deficits and amount of cell loss for time of maximal prenatal effect of the drug.