Shoham S, Ebstein R P
Shapiro Molecular Neurobiology Laboratory, S. Herzog Memorial Hospital, Jerusalem, Israel.
Exp Neurol. 1997 Oct;147(2):361-76. doi: 10.1006/exnr.1997.6622.
In the current study we employed immunohistochemical techniques to identify neuronal and glial cells in specific brain areas that modulate beta-amyloid precursor protein (betaAPP) synthesis following kainate-induced seizures. In addition, antibodies directed against the FOS protein, which is generated by activation of the immediate early gene c-fos and is temporally associated with ongoing seizure activity, were used to identify transneuronal pathways activated after kainate-induced seizures (KIS). It was therefore possible to correlate the appearance of activated neuronal pathways identified by FOS-like immunoreactivity (LI) and PAPP-LI in alternate sections. In addition, we employed immunohistochemical procedures to characterize morphological changes in neuronal and glial cells following kainate-induced seizures in both young and adult rats. Our results demonstrate a specific pattern of FOS-LI induced by kainate injection. In older animals FOS-LI spreads out from limbic cortical regions, including the piriform and entorhinal cortex, to other cortical regions, including the parietal and somatosensory cortices. Seizures were associated with decrease in neuronal betaAPP-LI in both young and adult rats, whereas glial betaAPP-LI markedly increased. The increase in betaAPP-LI glia was far more extensive in adult than in young rats and the anatomical distribution of betaAPP-LI glia was grossly correlated with FOS-LI. The spread of betaAPP-LI follows seizure-activated transsynaptic pathways. It is likely that the sequence of events following kainate injection is initially triggered by c-fos gene expression, which is rapidly followed by modulation of betaAPP synthesis in parallel to, or preceding, morphological changes of both microglia and astrocytes. The present study, which extensively characterized early changes in c-fos expression and betaAPP-LI in glia following kainate-induced seizures, is a potentially useful animal model for the in vivo study of numerous facets of betaAPP synthesis and the possible role of such processes in Alzheimer's disease.
在本研究中，我们采用免疫组织化学技术来识别特定脑区中的神经元和神经胶质细胞，这些脑区在海藻酸诱导的癫痫发作后调节β-淀粉样前体蛋白（βAPP）的合成。此外，针对FOS蛋白的抗体被用于识别海藻酸诱导的癫痫发作（KIS）后激活的跨神经元通路，FOS蛋白由即刻早期基因c-fos激活产生，且在时间上与正在进行的癫痫活动相关。因此，有可能将通过FOS样免疫反应性（LI）和PAPP-LI在相邻切片中识别出的激活神经元通路的出现情况进行关联。此外，我们采用免疫组织化学方法来描述幼年和成年大鼠在海藻酸诱导的癫痫发作后神经元和神经胶质细胞的形态学变化。我们的结果显示了海藻酸注射诱导的FOS-LI的特定模式。在成年动物中，FOS-LI从边缘皮质区域，包括梨状皮质和内嗅皮质，扩散到其他皮质区域，包括顶叶皮质和躯体感觉皮质。癫痫发作在幼年和成年大鼠中均与神经元βAPP-LI的减少相关，而神经胶质细胞βAPP-LI则显著增加。成年大鼠中βAPP-LI神经胶质细胞的增加比幼年大鼠更为广泛，且βAPP-LI神经胶质细胞的解剖分布与FOS-LI大致相关。βAPP-LI的扩散遵循癫痫激活的跨突触通路。海藻酸注射后的事件序列可能最初由c-fos基因表达触发，随后在小胶质细胞和星形胶质细胞形态变化的同时或之前，迅速伴随着βAPP合成的调节。本研究广泛描述了海藻酸诱导的癫痫发作后胶质细胞中c-fos表达和βAPP-LI的早期变化，是一个潜在有用的动物模型，可用于体内研究βAPP合成的多个方面以及这些过程在阿尔茨海默病中的可能作用。
