Ramchandran H, Rajadhyaksha Medha S
Department of Life Sciences, Sophia College for Women, Mumbai, Maharashtra, India.
Toxicol Int. 2012 May;19(2):153-7. doi: 10.4103/0971-6580.97215.
Lithium, a drug used extensively for treatment of bipolar disorders, has also been shown to be neuroprotective in vivo and in vitro. While gross teratogenic effects of lithium at higher doses have been reported, in view of its potential wider use, it is necessary to investigate its effects on tissue formation at relatively low doses of lithium where no apparent teratogenic effects on morphology are observed.
We have used retina of chick embryo to investigate its effects during neural histogenesis. Three major cellular events involved in retinal histogenesis have been monitored: Proliferation as measured by expression of proliferating cell nuclear antigen (PCNA); initiation of differentiation as observed by expression of p27/Kip1 expression; apoptosis as monitored by TdT-mediated dUTPX-nick end labeling.
We demonstrate that lithium at a dose of 60 mM has no effect on gross eye morphology; it disrupts histogenesis of chick retina by blocking proliferation, inducing apoptosis, and generating post mitotic cells prematurely.
锂是一种广泛用于治疗双相情感障碍的药物,在体内和体外均已显示出神经保护作用。虽然已有报道称高剂量锂具有明显的致畸作用,但鉴于其潜在的更广泛用途,有必要研究其在相对低剂量锂时对组织形成的影响,此时未观察到对形态学的明显致畸作用。
我们使用鸡胚视网膜来研究其在神经组织发生过程中的作用。监测了视网膜组织发生过程中涉及的三个主要细胞事件:通过增殖细胞核抗原(PCNA)表达测量的增殖;通过p27/Kip1表达观察到的分化起始;通过TdT介导的dUTP缺口末端标记监测的细胞凋亡。
我们证明,60 mM剂量的锂对眼睛总体形态没有影响;它通过阻断增殖、诱导细胞凋亡和过早产生有丝分裂后细胞来破坏鸡视网膜的组织发生。