Ontogeny of seizure-induced increases in BDNF immunoreactivity and TrkB receptor activation in rat hippocampus
Ontogeny of seizure-induced increases in BDNF immunoreactivity and TrkB receptor activation in rat hippocampus
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DOI：
10.1002/hipo.10190
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发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
McNamara, JO
中科院分区：
文献类型：
--
作者：
Danzer, SC;He, XP;McNamara, JO
本研究验证了这样一个假设：在大鼠海马中，癫痫持续状态诱导的脑源性神经营养因子（BDNF）蛋白的解剖学和发育模式与癫痫持续状态诱导的磷酸化Trk免疫反应性增加相一致，磷酸化Trk免疫反应性是TrkB受体激活的一种衡量指标。在出生后第22天（P22）的大鼠中，海人酸诱导的癫痫持续状态发生1天后，在海马的苔藓纤维通路中检测到磷酸化Trk免疫反应性显著增加。相反，在P8或P14大鼠中未检测到磷酸化Trk免疫反应性的变化。在P17大鼠中，再次在苔藓纤维通路中检测到中等水平的磷酸化Trk免疫反应性增加。与磷酸化Trk免疫反应性一样，在P22大鼠而非P14大鼠的苔藓纤维通路中检测到BDNF免疫反应性显著增加。在癫痫持续状态后的P17大鼠中发现了不一致的情况，即检测到BDNF显著增加，但磷酸化Trk免疫反应性未增加。癫痫持续状态后海马提取物的免疫沉淀和蛋白质印迹分析显示，P22大鼠中磷酸化TrkB增加，但TrkB免疫反应性未增加，从而证实并扩展了免疫组织化学的发现。虽然大多数发现支持该假设，但在P17的个体动物中发现了重要的不一致情况。总之，这些发现与以下观点一致：癫痫持续状态诱导的苔藓纤维中BDNF含量增加对于实现TrkB的激活是必要的，但不是充分的，这通过磷酸化Trk免疫反应性得以揭示。此外，这些结果首次描述了发育中的动物在癫痫发作诱导下BDNF蛋白增加和TrkB受体激活的特征。（C）2004威利 - 利斯公司
The present work tested the hypothesis that the anatomic and developmental patterns of status epilepticus-induced increases of brain-derived neurotrophic factor (BDNF) protein coincided with status epilepticus-induced increases of phospho-Trk immunoreactivity, a measure of TrkB receptor activation, in rat hippocampus. In P22 rats, robust increases of phospho-Trk immunoreactivity were detected in the mossy fiber pathway of the hippocampus one day following kainate-induced status epilepticus. Conversely, no change in phospho-Trk immunoreactivity was detected in P8 or P14 rats. In P17 rats, intermediate levels of increased phospho-Trk immunoreactivity were detected, again in the mossy fiber pathway. Like phospho-Trk immunoreactivity, marked increases of BDNF immunoreactivity were detected in the mossy fiber pathway of P22 but not P14 rats. Dissociations were found in P17 rats following status epilepticus in that striking increases of BDNF, but not phospho-Trk immunoreactivity were detected. Immunoprecipitation and Western blot analyses of hippocampal extracts after status epilepticus showed increased phospho-TrkB, but not TrkB immunoreactivity in P22 rats, thereby confirming and extending the immunohistochemical findings. While most of the findings support the hypothesis, important dissociations among individual animals at P17 were identified. Together the findings are consistent with the proposal that status epilepticus-induced increase of BDNF content in the mossy fibers is necessary, but not sufficient, to effect activation of TrkB, as revealed by phospho-Trk immunoreactivity. Furthermore, these results provide the first characterization of seizure-induced increases in BDNF protein and Trk13 receptor activation in developing animals. (C) 2004 Wiley-Liss, Inc.