Transient improvement in cognitive function and synaptic plasticity in rats following cancer chemotherapy
Transient improvement in cognitive function and synaptic plasticity in rats following cancer chemotherapy
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DOI：
10.1158/1078-0432.ccr-05-1286
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发表时间：
2006-01-01
影响因子：
11.5
通讯作者：
Ingram, DK
中科院分区：
文献类型：
--
作者：
Lee, GD;Longo, DL;Ingram, DK
背景：癌症化疗与认知障碍有关。有几个问题使这些发现复杂化，包括患者的健康，多种化疗药物的使用和正确的认知评估。为了控制这些因素，我们进行了认知研究的雌性大鼠接受环磷酰胺或5-氟尿嘧啶（5 FU）。方法：年轻（7个月）的雌性Fischer-344大鼠接受5次注射环磷酰胺（100 mg/kg），5 FU（150 mg/kg），或生理盐水腹腔注射。每4周，共18周。用环磷酰胺（80 mg/kg i. p.）16周恢复8 - 10周后，在两个迷宫学习任务中测试大鼠，Morris水迷宫和Stone 14单元T-迷宫。通过检查年轻环磷酰胺处理大鼠海马切片的长时程增强（LTP）来评估神经元突触功能。结果：尽管化疗引起了毒性作用，但与对照组相比，环磷酰胺和5 FU处理的大鼠表现出显着更好的迷宫表现。化疗恢复29至42周后，未观察到对迷宫表现的显著影响。在老年大鼠中，环磷酰胺治疗14周也产生毒性，但在16周恢复后，石迷宫学习没有受损。在环磷酰胺治疗期间进行评估时，受损的LTP的证据出现，然而，与8周的恢复后，5环磷酰胺治疗，我们观察到增强LTP。结论：尽管伴随化疗的毒性，没有证据表明认知功能受损后出现恢复。事实上，经过7到9周的恢复，我们注意到学习和LTP改善的证据。
Background: Cancer chemotherapy has been associated with cognitive impairment. Several issues complicate such findings including the patients' health, use of multiple chemotherapeutic agents, and proper assessment of cognition. To control these factors, we conducted cognitive studies in female rats receiving cyclophosphamide or 5-fluorouracil (5FU).Methods: Young (7 months) female Fischer-344 rats received five injections of cyclophosphamide (100 mg/kg), 5FU (150 mg/kg), or saline i.p. every 4 weeks for a total of 18 weeks. Aged (18 months) female Fischer-344 rats were treated with cyclophosphamide (80 mg/kg i.p.) for 16 weeks. After 8 to 10 weeks of recovery, rats were tested in two maze learning tasks, the Morris water maze and the Stone 14-unit T-maze. Neuronal synaptic function was assessed by examining long-term potentiation (LTP) in hippocampal slices obtained from young cyclophosphamide-treated rats.Results: Despite the toxic effects induced by chemotherapy, cyclophosphamide- and 5FU-treated rats showed significantly better maze performance compared with controls. Following 29 to 42 weeks of recovery from chemotherapy, no significant effects were observed on maze performance. In aged rats, cyclophosphamide treatment for 14 weeks also produced toxicity, but no impairment in Stone maze learning after 16 weeks of recovery. When assessed during cyclophosphamide treatment, evidence of impaired LTP emerged; however, with 8 weeks of recovery following five cyclophosphamide treatments, we observed enhanced LTP.Conclusion: Despite toxicity accompanying chemotherapy, no evidence of impaired cognitive performance emerged after recovery. Indeed, following 7 to 9 weeks of recovery, we noted evidence of improved learning and LTP.