Neuronal-Glial Interaction in the Treatment of Bipolar

现在有令人信服的证据表明，放射状胶质细胞不仅具有引导新生神经元的潜力，而且还具有自我更新和生成神经元和星形胶质细胞的潜力。最近的数据还表明，星形胶质细胞使中枢神经系统神经元上成熟的、有功能的突触数量增加了7倍，表明神经胶质细胞可以深刻地调节中枢神经系统突触的数量。神经胶质细胞还在调节突触谷氨酸水平、中枢神经系统能量平衡、营养因子释放等方面发挥重要作用，并与神经元形成动态、复杂的突触网络。然而，由于神经成像、死后形态测量和微阵列研究的融合，神经胶质功能障碍在主要精神疾病中的可能性直到最近才得到认真考虑，这些研究清楚地揭示了精神分裂症和情绪障碍中神经胶质细胞的异常。为了研究LI对神经胶质细胞和神经元生长的影响，我们建立了星形胶质细胞和神经元原代培养体系。 分别用或不加Li处理细胞。我们发现，锂促进了星形胶质细胞的增殖，它可能间接地(通过释放胶质细胞中的因子)调节神经元的分化。星形胶质细胞可诱导多能未成熟神经元表达星形胶质细胞表型。接下来，我们将研究星形胶质细胞中细胞信号的变化。 增殖和神经元分化研究Li诱导作用的可能分子机制此外，我们还将检测Li是否影响CNS中的另一种胶质细胞和星形胶质细胞前体少突胶质细胞的生长。我们的初步数据表明，Li促进了少突胶质细胞的增殖。这些机制可能为改善严重神经精神障碍的长期治疗提供一个潜在的靶点。

There is now compelling evidence that radial glial cells have the potential, not only to guide newly born neurons, but also to self-renew and to generate both neurons and astrocytes. Recent data has also shown that astrocytes increase the number of mature, functional synapses on CNS neurons by sevenfold, demonstrating that CNS synapse number can be profoundly regulated by glia. Glial cells are also known to play critical roles in regulating synaptic glutamate levels, CNS energy eostasis, liberation of trophic factors, and indeed form dynamic, complex synaptic networks with neurons. Nevertheless, the possibility of glial dysfunction in major psychiatric disorders has only recently received serious consideration due to the converging neuroimaging, postmortem morphometric and microarray studies, which have clearly revealed glial abnormalities in schizophrenia and mood disorders. To examine the effect of Li on glia and neuron growth, we have established astrocyte and neuronal primary culture system. Cells were treated with or without Li. We found that the astrocyte, whose proliferation is increased by lithium, may indirectly (via liberation of factors from glial cells) regulate neuronal differentiation. Astrocytes may induce the pluripotent immature neuron to express an astrocytic phenotype. Next, we will examine the alteration of cell signaling in astrocyte proliferation and neuronal differentiation to study the possible molecular mechanism of Li-induced action In addition, we will examine whether Li affects growth of oligodendricyte, another glia and precursor of astrocytes in CNS. Our preliminary data have demonstrated that that Li increased oligodendicytes proliferation. These mechanisms may provide a potential target for improved long-term therapeutics for severe neuropsychiatric disorders.