Effects of repeated minimal electroshock seizures on NGF, BDNF and FGF-2 protein in the rat brain during postnatal development
Effects of repeated minimal electroshock seizures on NGF, BDNF and FGF-2 protein in the rat brain during postnatal development
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DOI：
10.1016/j.ijdevneu.2010.02.003
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发表时间：
2010-05-01
影响因子：
1.8
通讯作者：
Kondratyev, Alexei
中科院分区：
文献类型：
--
作者：
Kim, Jinsook;Gale, Karen;Kondratyev, Alexei
反复短暂的癫痫发作，例如由电休克疗法（ECT）引起的癫痫发作，会显着提高成年大鼠大脑中的神经营养因子水平，但尚不清楚未成熟的动物是否也会出现类似的癫痫反应。为了解决这个问题，我们在出生后不同阶段的幼鼠中通过电惊厥（ECS）诱发短暂癫痫发作，并在选定的大脑区域检查碱性成纤维细胞生长因子（FGF-2）、神经生长因子（NGF）和脑源性神经营养因子（BDNF）蛋白，已知这些营养因子在成年大鼠中在 ECS 诱导癫痫发作后会增加。ECS 治疗每天（3 次/天）对大鼠进行，持续 7 天。三个不同年龄的幼崽：出生后 (P)1-7、P7-13 或 P14-20。最后一次 ECS 后 6 小时，使用鼻皮质中 FGF-2 的蛋白质印迹法测量蛋白质水平。对海马中的 BDNF 和 NGF 以及额叶皮层中的 NGF 进行 ELISA。P1-7 期间重复 ECS 诱导的癫痫发作 7 天不会改变 BDNF 的蛋白水平。 FGF-2，或 NGF。 P7-13 期间的重复癫痫发作仅影响 BDNF 蛋白，导致海马体比假治疗对照组显着升高 40%。在 P14-20 幼犬中，反复癫痫发作导致海马 BDNF 显着增加（比对照组高出 162%），鼻皮质中 FGF-2 显着增加（比对照组高出 34%），而 NGF 蛋白在海马或额叶皮层中没有显示出显着变化。结果表明，在出生后第一周，对癫痫引起的神经营养因子增加有抵抗力，但到出生后第三周，BDNF 和 FGF-2 均显着增加。 FGF-2 因反复癫痫发作而显着升高。这种时间依赖性特征表明，这些蛋白质的合成最初是与活性无关的，到 3 周龄时变得受活性依赖性调节的影响。癫痫发作引起的营养因子变化的成熟可能对于理解 ECT 和儿童癫痫发作的影响很重要。 (C) 2010 ISDN。由爱思唯尔有限公司出版。保留所有权利。
Repeated brief seizures, such as those induced by electroconvulsive therapy (ECT), markedly elevate neurotrophic factor levels in the adult rat brain, but it is not known whether a similar response to seizures occurs in immature animals. To address this question, we evoked brief seizures with electroconvulsive shock (ECS) in rat pups at different stages of postnatal development and examined basic fibroblast growth factor (FGF-2), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) proteins in selected brain regions in which these trophic factors are known to increase in the adult rat following ECS-induced seizures.ECS treatments were administered daily (3 episodes/day) over 7 days to rat pups of three different ages: postnatal day (P)1-7, P7-13, or P14-20. Protein levels were measured 6 h after the last ECS using Western blotting for FGF-2 in rhinal cortex. ELISA for BDNF and NGF in hippocampus, and NGF in frontal cortex.7 days of repeated ECS-induced seizures during P1-7 did not alter protein levels for BDNF. FGF-2, or NGF. The repeated seizures during P7-13 affected only BDNF protein, causing a significant elevation of 40% in hippocampus over sham-treated controls. In P14-20 pups, the repeated seizures resulted in a significant increase in BDNF in hippocampus (162% over controls) and FGF-2 in rhinal cortex (34% over controls), while NGF protein did not show a significant change in either hippocampus or frontal cortex.The results suggest that during the first postnatal week there is a resistance to seizure-induced increase in neurotrophic factors, but by the third postnatal week, both BDNF and FGF-2 are elevated substantially in response to repeated seizures. This time-dependent profile suggests that synthesis of these proteins is initially activity-independent, becoming subject to activity-dependent regulation by 3 weeks of age. This maturation of seizure-evoked changes in trophic factors may be important for understanding the impact of ECT and seizures in childhood. (C) 2010 ISDN. Published by Elsevier Ltd. All rights reserved.