ELEVATED SEIZURE THRESHOLD AND IMPAIRED SPATIAL-LEARNING IN TRANSGENIC MICE WITH PUTRESCINE OVERPRODUCTION IN THE BRAIN
ELEVATED SEIZURE THRESHOLD AND IMPAIRED SPATIAL-LEARNING IN TRANSGENIC MICE WITH PUTRESCINE OVERPRODUCTION IN THE BRAIN
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DOI：
10.1111/j.1460-9568.1993.tb00978.x
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发表时间：
1993-09-01
影响因子：
3.4
通讯作者：
RIEKKINEN, PJ
中科院分区：
文献类型：
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作者：
HALONEN, T;SIVENIUS, J;RIEKKINEN, PJ
我们已经研究了腐胺的作用，通过使用转基因小鼠品系过表达人类鸟氨酸脱羧酶基因在其大部分组织。转基因的异常表达在大脑中表现得最明显，导致腐胺含量增加高达20倍。我们报告说，腐胺在所有的大脑区域（皮质，纹状体，海马和小脑）的转基因小鼠分析显示出显着升高的癫痫发作阈值化学和电刺激，并在空间学习和记忆测试的性能受损。腐胺可能是这些变化的主要原因，这一观点得到了以下事实的支持：大脑中主要神经递质氨基酸谷氨酸和GABA的浓度在转基因动物中没有改变，并且发现通过抑制L-鸟氨酸的催化作用而实现的大脑腐胺的进一步增加似乎对电击诱导的癫痫发作提供了额外的保护。这些结果表明，通常观察到的鸟氨酸脱羧酶活性的增加和脑腐胺的大量增加与神经元损伤是一种神经保护措施，而不是损害的原因。
We have studied the role of putrescine by using transgenic mouse lines overexpressing the human ornithine decarboxylase gene in most of their tissues. The aberrant expression of the transgene is most strikingly manifested in the brain, leading to an increase of up to 20-fold in putrescine content. We report that the transgenic mice with grossly elevated putrescine in all brain regions analysed (cortex, striatum, hippocampus and cerebellum) showed a significantly elevated seizure threshold to chemical and electrical stimuli, and impaired performance in spatial learning and memory tests. The view that putrescine may be primarily responsible for these changes was supported by the fact that the concentrations of the major neurotransmitter amino acids, glutamate and GABA in the brain, were not changed in the transgenic animals, and by the finding that a further increase in brain putrescine, achieved by inhibition of the catabolism of L-ornithine, appeared to provide additional protection against electroshock-induced seizures. These results suggest that the commonly observed increase in ornithine decarboxylase activity and the massive increase in brain putrescine in connection with neuron damage is a neuroprotective measure rather than a cause of the damage.