Mignone Robert G, Weber E Todd
Department of Biochemistry, Rider University, Lawrenceville, NJ 08648 USA.
Brain Res. 2006 Sep 21;1111(1):26-9. doi: 10.1016/j.brainres.2006.06.093. Epub 2006 Aug 1.
Antimitotic drugs used in the chemotherapeutic treatment of cancers induce undesirable but unavoidable side-effects from interruption of normal mitotic processes throughout the body. We have examined whether several such drugs capable of penetrating the blood-brain barrier - thioTEPA and 5-fluorouracil - influence the normal process of cell proliferation underlying neurogenesis in the dentate gyrus of the hippocampus of mice. thioTEPA was found to yield a pronounced dose-related inhibition in cell proliferation, while 5-fluorouracil did not. The magnitude of the inhibition paired with a lack of observable impairment of health in mice indicates a suitable experimental model for elucidating the contributions of hippocampal cell proliferation to cognition and behavior.
用于癌症化疗的抗有丝分裂药物会因干扰全身正常的有丝分裂过程而产生不良但不可避免的副作用。我们研究了几种能够穿透血脑屏障的此类药物——噻替派和5-氟尿嘧啶——是否会影响小鼠海马齿状回神经发生过程中细胞增殖的正常进程。结果发现噻替派会对细胞增殖产生明显的剂量相关抑制作用，而5-氟尿嘧啶则不会。这种抑制程度与小鼠未观察到的健康损害表明，这是一个用于阐明海马体细胞增殖对认知和行为贡献的合适实验模型。
