Long-term cognitive dysfunction in the rat following docetaxel treatment is ameliorated by the phosphodiesterase-4 inhibitor, rolipram
Long-term cognitive dysfunction in the rat following docetaxel treatment is ameliorated by the phosphodiesterase-4 inhibitor, rolipram
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DOI：
10.1016/j.bbr.2015.04.044
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发表时间：
2015-09-01
影响因子：
2.7
通讯作者：
O'Mara, Shane M.
中科院分区：
文献类型：
--
作者：
Callaghan, Charlotte K.;O'Mara, Shane M.
临床研究报告了连续化疗后长期认知和其他缺陷的证据，这通常被称为“化学雾”或“化学雾”。这些损伤的神经基础知之甚少。在这里，我们假设全身化疗治疗引起长期的神经行为缺陷，并且这些缺陷通过PDE 4抑制剂咯利普兰对cAMP的操纵而逆转。或对照溶液（乙醇/吐温20/0.9%生理盐水-5/5/90），每周一次，持续4周。让它们恢复4周，然后开始给予咯利普兰（0.5 mg/kg po）或溶媒（枫糖浆），每天持续4周。在治疗方案结束时，动物进行了测试的空间和识别记忆缺陷的对象探索任务和抑郁和焦虑样行为的强迫游泳测试（FST）和开放领域exploration.We报告多西他赛治疗受损的空间记忆，但不对象识别记忆，与对照组大鼠相比。多西他赛治疗的大鼠在FST中的不动时间也显著长于对照组。长期咯利普兰治疗减弱了所有这些与紫杉醇相关的变化，恢复了空间记忆并减少了不动性。总之，紫杉醇治疗的大鼠表现出空间记忆和抑郁样行为的改变，这是逆转后，长期咯利普兰管理。这些结果检测了多西他赛治疗后的长期认知和情绪变化，并将PDE 4抑制确定为与“化学因子”相关的神经心理学变化的靶向治疗。(C)2015 Elsevier B. V.版权所有。
Clinical studies report evidence of long-term cognitive and other deficits following adjunctive chemotherapy treatment, which is often termed "chemobrain" or "chemo-fog". The neurological bases of these impairments are poorly understood. Here, we hypothesize that systemic chemotherapy treatment causes long-term neurobehavioral deficits, and that these deficits are reversed by manipulation of cAMP by the PDE4 inhibitor, rolipram.Male han Wistar rats were treated with docetaxel (an adjunctive chemotherapeutic agent (1 mg/kg i.v.)) or control solution (ethanol/Tween 20/0.9% Saline - 5/5/90) once per week for 4 weeks. They were allowed to recover for 4 weeks, administration of rolipram (0.5 mg/kg po) or vehicle (maple syrup) then began and continued daily for 4 weeks. At the end of the treatment regime animals were tested for spatial and recognition memory deficits with the object exploration task and for depressive- and anxiety-like behavior in the forced swim test (FST) and open field exploration.We report docetaxel treatment impaired spatial memory but not object recognition memory, compared to control rats. Docetaxel-treated rats also spent significantly more time immobile than controls in the FST. Chronic rolipram treatment attenuated all of these docetaxel-associated changes, recovering spatial memory and reducing immobility. In conclusion, docetaxel-treated rats exhibit alterations in spatial memory and depressive-like behavior, which are reversed following chronic rolipram administration. These results detect long-term cognitive and mood changes following docetaxel treatment and identify PDE4 inhibition as a target treatment of neuropsychological changes associated with "chemobrain". (C) 2015 Elsevier B.V. All rights reserved.