Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death
Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death
复制标题
DOI：
10.1073/pnas.260501697
复制
发表时间：
2000-12-19
影响因子：
11.1
通讯作者：
Ceccatelli, S
中科院分区：
文献类型：
--
作者：
Ahlbom, E;Gogvadze, V;Ceccatelli, S
人们越来越担心，产前接触过量的糖皮质激素可能会对包括神经系统在内的各种器官的发育产生有害影响。这项研究旨在评估产前暴露于高水平的糖皮质激素是否会对神经细胞的存活产生长期影响。妊娠大鼠腹腔注射。从妊娠第14天开始给予0.1 mg/kg的地塞米松(DEX)，取1周龄大鼠的小脑颗粒细胞(CGC)。培养7天后，细胞暴露在过氧化氢、甲基汞或秋水仙碱中，浓度达到已知的诱导细胞凋亡的浓度。暴露于过氧化氢或甲基汞后，DEX-CGC的细胞凋亡率显著高于对照组-CGC，因为线粒体在细胞凋亡中起关键作用，研究了线粒体的功能，发现DEX-CGC中诱导线粒体通透性转换所需的Ca~(2+)阈值水平、Ca~(2+)积累率和氧耗均降低。此外，DEX-CGC中抗氧化物酶过氧化氢酶的活性显著降低。新生和40日龄DEX大鼠小脑匀浆中的过氧化氢酶活性也有类似的下降。总之，这些结果表明，产前暴露于高水平的糖皮质激素会导致CGC的长期变化，使其对氧化应激更加敏感。随着多剂量糖皮质激素在早产儿中的使用越来越多，产前接触过量糖皮质激素可能导致长期的神经后果成为一个相关的问题。
There is growing concern that prenatal exposure to excessive glucocorticoids may have deleterious effects on the development of various organs, including the nervous system. This study aimed at evaluating whether prenatal exposure to high levels of glucocorticoids might produce long-term effects on neuronal cell survival. Pregnant rats were injected i.p. with 0.1 mg/kg dexamethasone (DEX) from day 14 postconception, and cerebellar granule cells (CGC) were prepared from 1-week-old rats from DEX-treated and control dams. After 7 days in culture, cells were exposed to H2O2, methylmercury, or colchicine at concentrations known to induce apoptotic cell death. After exposure to H2O2 or methylmercury, both inducing oxidative stress, the number of apoptotic cells was significantly higher in DEX- than in control-CGC Because mitochondria play a key role in apoptosis, mitochondrial function was investigated, and a decrease in the threshold level of Ca2+ necessary for induction of mitochondrial permeability transition, in Ca2+ accumulation rate, and in oxygen consumption was detected in DEX-CGC. Moreover, the activity of the antioxidant enzyme catalase was significantly decreased in DEX-CGC. A similar decrease in catalase activity was observed in cerebellar homogenate from newborn and 40-day-old DEX-rats. In conclusion, these results indicate that prenatal exposure to high levels of glucocorticoids induces long-lasting changes in CGC rendering them more sensitive to oxidative stress. With the increasing use of multiple doses of glucocorticoids in preterm infants, the possibility that prenatal exposure to excess glucocorticoids may lead to long-term neurological consequences becomes a relevant issue.