Feinstein D L
NeuroAnesthesia Research, University of Illinois at Chicago 60607, USA.
J Neurochem. 1998 Aug;71(2):883-6. doi: 10.1046/j.1471-4159.1998.71020883.x.
The mechanisms underlying the antimanic effects of lithium are largely unknown but may involve long-term changes in brain gene expression. To determine if lithium could modify gene expression in astrocytes, the predominant cell type in brain, we tested the effects of LiCl on expression of nitric oxide synthase type 2 (NOS-2) in cultured glial cells. Incubation of primary rat astrocytes with endotoxin [lipopolysaccharide (LPS)] and proinflammatory cytokines induced NOS-2 gene and protein expression, as assessed by nitrite production and measurement of L-citrulline synthesis in whole cell lysates. Incubation with LiCl, but not KCl, increased NOS-2 activity up to 1.6-fold. LiCl also potentiated (up to 2.7-fold) the induction of NOS-2 expression by LPS plus interferon-gamma in C6 glioma cells but had little effect on LPS-induced nitrite accumulation from mouse RAW 264.7 macrophages. LiCl increased NOS-2 mRNA steady-state levels, suggesting an effect on mRNA stability and/or NOS-2 gene transcription. These results demonstrate that LiCl can modify astroglial gene expression and suggest that chronic treatment with lithium could exacerbate inflammatory responses in brain glial cells.
锂盐抗躁狂作用的潜在机制很大程度上尚不清楚，但可能涉及大脑基因表达的长期变化。为了确定锂盐是否能改变大脑中主要细胞类型星形胶质细胞的基因表达，我们测试了氯化锂对培养的神经胶质细胞中2型一氧化氮合酶（NOS-2）表达的影响。用内毒素[脂多糖（LPS）]和促炎细胞因子孵育原代大鼠星形胶质细胞可诱导NOS-2基因和蛋白表达，这通过亚硝酸盐生成和全细胞裂解物中L-瓜氨酸合成的测量来评估。用氯化锂而非氯化钾孵育可使NOS-2活性提高至1.6倍。氯化锂还增强了（高达2.7倍）LPS加干扰素-γ对C6胶质瘤细胞中NOS-2表达的诱导作用，但对LPS诱导的小鼠RAW 264.7巨噬细胞中亚硝酸盐积累影响很小。氯化锂增加了NOS-2 mRNA的稳态水平，表明其对mRNA稳定性和/或NOS-2基因转录有影响。这些结果表明氯化锂可改变星形胶质细胞的基因表达，并提示锂盐的长期治疗可能会加剧大脑神经胶质细胞的炎症反应。
