Keshavarz Mojtaba, Emamghoreishi Masoumeh, Nekooeian Ali Akbar, J Warsh Jerry, Zare Hamid Reza
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;
Iran J Med Sci. 2013 Sep;38(3):255-62.
B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has been implicated in lithium's neuroprotective effect. However, most studies have focused on assessing the effects of lithium in neurons, ignoring examination of bcl-2 in astrocytes, which also influence neuronal survival and are affected in bipolar disorder. The aim of this study was to evaluate whether chronic lithium treatment also elevates bcl-2 expression in astrocytes compared with neuronal and mixed neuron-astrocyte cultures.
Rat primary astrocyte, neuronal, and mixed neuron-astrocyte cultures were prepared from the cerebral cortices of 18-day embryos. The cell cultures were treated with lithium (1 mM) or vehicle for 24 h or 7 days. Thereafter, bcl-2 mRNA and protein levels were determined by RT-PCR and ELISA, respectively.
Chronic, but not acute, lithium treatment significantly increased bcl-2 protein levels in the astrocyte cultures compared with the vehicle-treated cultures. While lithium treatment increased bcl-2 protein levels in both neuronal and mixed neuron-astrocyte cultures, the elevations fell short of statistical significance compared with the respective vehicle-treated cultures. However, neither acute nor chronic lithium treatment affected bcl-2 mRNA levels in any of the three cell types studied.
Increased bcl-2 levels in rat primary astrocyte cultures following chronic lithium treatment suggest astrocytes are also a target of lithium's action. In light of the evidence showing decreased numbers of glial cells in the post-mortem brain of patients bipolar disorder with and increased glial numbers following lithium treatment, the findings of this study indicate that lithium's action on astrocytes may account, at least in part, for its therapeutic effects in bipolar disorder.
B细胞淋巴瘤/白血病-2蛋白（bcl-2）是一种重要的抗凋亡因子，与锂的神经保护作用有关。然而，大多数研究都集中在评估锂对神经元的影响，而忽略了对星形胶质细胞中bcl-2的检测，星形胶质细胞也会影响神经元的存活，并且在双相情感障碍中会受到影响。本研究的目的是评估与神经元培养物和神经元-星形胶质细胞混合培养物相比，慢性锂治疗是否也能提高星形胶质细胞中bcl-2的表达。
从18天胚胎的大脑皮层制备大鼠原代星形胶质细胞、神经元和神经元-星形胶质细胞混合培养物。细胞培养物用锂（1 mM）或溶剂处理24小时或7天。此后，分别通过逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）测定bcl-2 mRNA和蛋白水平。
与溶剂处理的培养物相比，慢性而非急性锂处理显著提高了星形胶质细胞培养物中bcl-2蛋白水平。虽然锂处理增加了神经元和神经元-星形胶质细胞混合培养物中bcl-2蛋白水平，但与各自的溶剂处理培养物相比，升高未达到统计学意义。然而，急性和慢性锂处理均未影响所研究的三种细胞类型中任何一种的bcl-2 mRNA水平。
慢性锂处理后大鼠原代星形胶质细胞培养物中bcl-2水平升高表明星形胶质细胞也是锂作用的靶点。鉴于有证据表明双相情感障碍患者死后大脑中的胶质细胞数量减少，而锂治疗后胶质细胞数量增加，本研究结果表明锂对星形胶质细胞的作用可能至少部分解释了其在双相情感障碍中的治疗效果。
