Department of Clinical Biochemistry and Pharmacology (Ms Kara and Dr Agam), and Psychiatry Research Unit (Ms Kara and Drs Belmaker and Agam), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Mental Health Center, Beer-Sheva, Israel (Ms Kara and Dr Agam); Tel Aviv-Yaffo Academic College, Tel Aviv-Yaffo, Israel (Ms Kara and Dr Einat); Tata Institute of Fundamental Research, Mumbai, India (Ms Narayanan and Dr Vaidya); University of Minnesota, Minneapolis, Minnesota (Dr Einat).
Int J Neuropsychopharmacol. 2015 Jan 29;18(7):pyv003. doi: 10.1093/ijnp/pyv003.
The term adult neurogenesis constitutes a series of developmental steps including the birth, survival, differentiation, maturation, and even death of newborn progenitor cells within neurogenic niches. Within the hippocampus progenitors reside in the neurogenic niche of the subgranular zone in the dentate gyrus subfield. At the different stages, designated type-I, type-IIa, type-IIb, type-III, and granule cell neurons, the cells express a series of markers enabling their identification and visualization. Lithium has been shown to increase hippocampal cell proliferation in the subgranular zone of the hippocampal dentate gyrus subfield of adult rodents and to stimulate the proliferation of hippocampal progenitor cells in vitro, but data regarding lithium's ability to increase neuronal differentiation and survival is equivocal.
To clarify the effect of lithium on adult hippocampal neurogenesis, we identified the effect of chronic lithium treatment on distinct stages of hippocampal progenitor development using adult Nestin-green fluorescent protein transgenic mice and immunofluorescent techniques.
The present observations confirm that lithium targets the initial stages of progenitor development enhancing the turnover of quiescent neural progenitors/putative stem-cells, corroborating previous reports. However, the enhanced quiescent neural progenitor-turnover does not translate into an increased number of immature neurons. We also observed a steep decline in the number of type-III immature neurons with complex tertiary-dendrites, suggesting that lithium alters the morphological maturation of newborn neurons.
Our results do not corroborate previous reports of lithium-induced enhanced numbers of newly generated neurons.
成人神经发生是一系列发育步骤的总称，包括神经发生龛内新生祖细胞的出生、存活、分化、成熟，甚至死亡。在海马体中，祖细胞存在于齿状回颗粒下区的神经发生龛内。在不同阶段，即 I 型、IIa 型、IIb 型、III 型和颗粒细胞神经元，细胞表达一系列标记物，使其能够被识别和可视化。锂已被证明可以增加成年啮齿动物海马齿状回颗粒下区的海马细胞增殖，并刺激海马祖细胞在体外增殖，但关于锂增加神经元分化和存活的能力的数据尚无定论。
为了阐明锂对成年海马神经发生的影响，我们使用成年巢蛋白-绿色荧光蛋白转基因小鼠和免疫荧光技术，确定慢性锂处理对海马祖细胞发育不同阶段的影响。
本研究观察结果证实，锂作用于祖细胞发育的初始阶段，增强静止神经祖细胞/潜在干细胞的更替，与之前的报道一致。然而，增强的静止神经祖细胞更替并没有转化为更多的未成熟神经元数量。我们还观察到具有复杂三级树突的 III 型未成熟神经元数量急剧下降，表明锂改变了新生神经元的形态成熟。
我们的结果与锂诱导新生成神经元数量增加的先前报道不一致。
