Gall C, Lauterborn J, Bundman M, Murray K, Isackson P
Department of Anatomy, University of California, Irvine 92717.
Epilepsy Res Suppl. 1991;4:225-45.
Seizure-induced plasticity, in the form of either changes in cellular morphology or changes in neurochemistry, could have a profound impact upon regional excitability in brain. There is now ample evidence that in genetically 'normal' animals, seizure activity stimulates alterations in neuronal gene expression which could lead to changes in levels of excitability and, hence, to changes in the susceptibility for further seizures. Here we describe the influence of limbic seizures upon the expression of nerve growth factor (NGF), 2 related neurotrophic factors, brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3), and several neuropeptides (enkephalin, dynorphin, and neuropeptide Y) in the rat forebrain. Using 35S-labeled riboprobes and in situ hybridization methods, the effects of recurrent limbic seizures and of individual hippocampal paroxysmal discharges have been evaluated. Recurrent seizures are found to increase levels of mRNAs for NGF and BDNF and to decrease levels of mRNA for NT3 within select hippocampal neurons. Temporally distinct increases in the expression of mRNAs for NGF and BDNF are also observed across broad fields of neocortex, paleocortex (entorhinal, piriform, and cingulate cortices), and the amygdala. As little as one 20-sec paroxysmal discharge is sufficient to stimulate large changes in neurotrophic factor mRNA content of hippocampal neurons. The time courses and cellular specificities of these alterations in neurotrophic factor expression are discussed and contrasted with seizure-induced changes in neuropeptide expression. Mechanisms by which seizure-induced increases in hippocampal neuropeptide and neurotrophic factor synthesis could lead to both short- and long-term changes in regional excitability, and thereby could contribute to susceptibility for further seizure activity, are considered.
癫痫发作诱导的可塑性，表现为细胞形态变化或神经化学变化，可能会对大脑区域兴奋性产生深远影响。现在有充分证据表明，在基因“正常”的动物中，癫痫活动会刺激神经元基因表达的改变，这可能导致兴奋性水平的变化，进而导致对进一步癫痫发作易感性的改变。在此，我们描述边缘性癫痫发作对大鼠前脑神经营养因子（NGF）、2种相关神经营养因子、脑源性神经营养因子（BDNF）和神经营养素3（NT3）以及几种神经肽（脑啡肽、强啡肽和神经肽Y）表达的影响。使用35S标记的核糖探针和原位杂交方法，评估了复发性边缘性癫痫发作和单个海马阵发性放电的影响。发现复发性癫痫发作会增加特定海马神经元内NGF和BDNF的mRNA水平，并降低NT3的mRNA水平。在新皮层、古皮层（内嗅、梨状和扣带回皮层）和杏仁核的广泛区域也观察到NGF和BDNF的mRNA表达在时间上有明显增加。仅一次20秒的阵发性放电就足以刺激海马神经元神经营养因子mRNA含量的大幅变化。讨论了这些神经营养因子表达变化的时间进程和细胞特异性，并与癫痫发作诱导的神经肽表达变化进行了对比。考虑了癫痫发作诱导的海马神经肽和神经营养因子合成增加可能导致区域兴奋性短期和长期变化，从而可能导致对进一步癫痫活动易感性增加的机制。
