Gilad Gad M, Gilad Varda H
Research and Development, Laboratory for Neuroscience, Assaf Harofeh Medical Center, Zrifin, Israel.
Brain Res. 2002 Jul 5;943(1):23-9. doi: 10.1016/s0006-8993(02)02479-4.
Recent findings indicate that rapid and transient changes in polyamine metabolism, termed the polyamine-stress-response, may occur repeatedly in the brain after chronic intermittent stress. Here, we sought to examine the effects of chronic intermittent restraint stress, or of daily intraperitoneal dexamethasone injections on polyamine concentrations in the hippocampus of adult male C57BL/6 mice. Additionally, we studied the effects of alpha-difluoromethylornithine, an irreversible ornithine decarboxylase inhibitor, on stress-induced changes in polyamines and on behavioral reactivity to novelty stress measured in an open-field arena. As previously observed, following a single stress episode putrescine concentration increased transiently, but the polyamines spermidine and spermine remained unchanged. Following chronic restraint stress, putrescine concentration was increased after each daily stress episode with the largest increase observed after the 4th episode, while spermidine was increased just after the 2nd and 4th episodes and spermine only after the 4th daily episode. In contrast, all polyamine concentrations were increased after 10 injections of either dexamethasone or vehicle (0.9% NaCl). A 14-day course of alpha-difluoromethylornithine treatment resulted in a complete putrescine depletion and over 50% reduction in polyamines, and led to changes in open field activity indicative of altered emotional behavior.
(a) while putrescine concentration increases in the hippocampus after each restraint stress episode, spermidine and spermine undergo a delayed but transient increase; (b) in contrast, chronic dexamethasone treatment may lead to a permanent increase in the concentrations of all polyamines and; (c) chronic alpha-difluoromethylornithine treatment reduces brain polyamine concentrations and modulates emotional reactivity to novelty stress. The study indicates that the brain polyamine-stress-response is a dynamic process that varies with the type, intensity and length of stressful stimuli, and implicates this response as an adaptive mechanism in the reaction to stressors.
最近的研究结果表明，多胺代谢中快速且短暂的变化，即所谓的多胺应激反应，在慢性间歇性应激后可能会在大脑中反复出现。在此，我们试图研究慢性间歇性束缚应激或每日腹腔注射地塞米松对成年雄性C57BL/6小鼠海马体中多胺浓度的影响。此外，我们研究了不可逆的鸟氨酸脱羧酶抑制剂α-二氟甲基鸟氨酸对应激诱导的多胺变化以及在旷场实验中测量的对新异应激行为反应性的影响。如先前观察到的，在单次应激事件后，腐胺浓度短暂升高，但亚精胺和精胺保持不变。在慢性束缚应激后，每日应激事件后腐胺浓度均升高，第4次事件后升高幅度最大，而亚精胺仅在第2次和第4次事件后升高，精胺仅在第4次每日事件后升高。相比之下，在注射10次地塞米松或溶剂（0.9%氯化钠）后，所有多胺浓度均升高。为期14天的α-二氟甲基鸟氨酸治疗导致腐胺完全耗尽且多胺减少超过50%，并导致旷场活动变化表明情绪行为改变。
（a）每次束缚应激事件后海马体中腐胺浓度升高，而亚精胺和精胺经历延迟但短暂的升高；（b）相比之下，慢性地塞米松治疗可能导致所有多胺浓度永久性升高；（c）慢性α-二氟甲基鸟氨酸治疗降低脑多胺浓度并调节对新异应激的情绪反应性。该研究表明，脑多胺应激反应是一个动态过程，随应激刺激的类型、强度和持续时间而变化，并暗示这种反应是对应激源反应中的一种适应性机制。
