Enhancement of hippocampal neurogenesis by lithium
Enhancement of hippocampal neurogenesis by lithium
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DOI：
10.1046/j.1471-4159.2000.0751729.x
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发表时间：
2000-10-01
影响因子：
4.7
通讯作者：
Manji, HK
中科院分区：
文献类型：
--
作者：
Chen, G;Rajkowska, G;Manji, HK
越来越多的证据表明，情绪障碍与中枢神经系统局部体积减小以及神经元和神经胶质细胞萎缩或缺失有关。锂是治疗情绪障碍的主要药物，最近已被证明能显著提高啮齿动物大脑区域以及培养细胞中具有细胞保护作用的B细胞淋巴瘤蛋白 - 2（bcl - 2）的水平。鉴于bcl - 2的抗凋亡和神经营养作用，本研究旨在确定锂是否影响成年啮齿动物海马体的神经发生。小鼠长期接受锂治疗，并在12天内用5 - 溴 - 2 - 脱氧尿苷（BrdU）对分裂细胞进行标记。在最后一次注射后1天进行免疫组织化学分析，三维体视学细胞计数显示，锂使齿状回中BrdU标记的细胞显著增加了25%。进行了双标记免疫荧光研究，以将BrdU阳性细胞与神经元特异性核蛋白共定位，结果显示约65%的细胞为双标记。这些结果进一步充实了越来越多的证据，表明情绪稳定剂和抗抑郁药具有神经营养作用，因此可能用于其他神经精神疾病的长期治疗。
Increasing evidence suggests that mood disorders are associated with a reduction in regional CNS volume and neuronal and glial cell atrophy or loss. Lithium, a mainstay in the treatment of mood disorders, has recently been demonstrated to robustly increase the revels of the cytoprotective B-cell lymphoma protein-2 (bcl-2) in areas of rodent brain and in cultured cells. In view of bcl-2's antiapoptotic and neurotrophic effects, the present study was undertaken to determine if lithium affects neurogenesis in the adult rodent hippocampus. Mice were chronically treated with lithium, and 5-bromo-2-deoxyuridine (BrdU) labeling of dividing cells was conducted over 12 days. Immunohistochemical analysis was undertaken 1 day after the last injection, and three-dimensional stereological cell counting revealed that lithium produced a significant 25% increase in the BrdU-labeled cells in the dentate gyrus. Double-labeling immunofluorescence studies were undertaken to co-localize BrdU-positive cells with neuron-specific nuclear protein and showed that similar to 65% of the cells were double-labeled. These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders.