Hammonds Michael D, Shim Seong S, Feng Pingfu, Calabrese Joseph R
Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
Basic Clin Pharmacol Toxicol. 2007 May;100(5):356-9. doi: 10.1111/j.1742-7843.2007.00058.x.
Although it has been proposed that exposure to lithium up-regulates brain-derived neurotrophic factor (BDNF), B-cell leukaemia/lymphoma 2 protein (Bcl-2) and cyclic AMP-response element-binding protein (CREB), and these molecules are involved in the neuroplastic actions and clinical efficacy of the drug, the several lines of evidence suggest that the lithium-induced up-regulation of these molecules has not been consistently confirmed. Few studies have examined the effects of lithium exposure on the regulation of these molecules in the dentate gyrus (DG) and area CA1 in the hippocampus. We examined the effects of subchronic lithium treatment on the levels of BDNF, Bcl-2 and phosphorylated CREB in the DG and area CA1. We administered LiCl intraperitoneally (1 mEq/kg per day) to adult rats for 14 days, killed animals in 24 hr after the last administration of the drug, and determined the tissue levels of BDNF, Bcl-2 and pCREB in the DG and area CA1. Subchronic lithium treatment for 14 days did not significantly alter the levels of BDNF, Bcl-2 or phosphorylated CREB in the DG and area CA1 in the hippocampus. This study indicates that the lithium-induced up-regulation of these molecules may be various depending on the duration of lithium exposure and particular brain regions exposed to the drug.
尽管有人提出，锂暴露可上调脑源性神经营养因子（BDNF）、B细胞淋巴瘤2蛋白（Bcl-2）和环磷酸腺苷反应元件结合蛋白（CREB），且这些分子参与了该药物的神经可塑性作用及临床疗效，但多项证据表明，锂诱导的这些分子上调并未得到一致证实。很少有研究考察锂暴露对海马齿状回（DG）和CA1区这些分子调节的影响。我们研究了亚慢性锂治疗对DG和CA1区BDNF、Bcl-2和磷酸化CREB水平的影响。我们对成年大鼠腹腔注射氯化锂（每天1 mEq/kg），持续14天，在末次给药后24小时处死动物，并测定DG和CA1区BDNF、Bcl-2和pCREB的组织水平。亚慢性锂治疗14天并未显著改变海马DG和CA1区BDNF、Bcl-2或磷酸化CREB的水平。这项研究表明，锂诱导的这些分子上调可能因锂暴露的持续时间和药物作用的特定脑区而异。
