Neuronal-Glial Interaction in the Treatment of Bipolar

双相情感障碍治疗中的神经元-胶质细胞相互作用

• 批准号: 6824400
• 负责人: HUSSEINI K MANJI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6824400
• 关键词: astrocytes; bipolar depression; cell cell interaction; cell proliferation; central nervous system; glia; human tissue; lithium; mental disorder chemotherapy; neural transmission; neurogenesis; neurons; neuropsychology; neuroregulation; oligodendroglia; pharmacokinetics; tissue /cell culture

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.

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，星形胶质细胞增加了7倍的CNS神经元上的成熟的功能性突触的数量，表明CNS突触的数量可以被神经胶质细胞深刻地调节。还已知神经胶质细胞在调节突触谷氨酸水平、CNS能量平衡、营养因子释放中起关键作用，并且确实与神经元形成动态的复杂突触网络。然而，神经胶质功能障碍的可能性，主要精神疾病最近才得到认真考虑，由于收敛的神经影像学，死后形态和微阵列研究，这清楚地揭示了神经胶质异常的精神分裂症和情绪障碍。为了研究锂对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的原代培养系统。 用或不用Li处理细胞。我们发现，星形胶质细胞，其增殖增加的锂，可能间接（通过释放因子从神经胶质细胞）调节神经元分化。星形胶质细胞可以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改变， 增殖和神经元分化，以研究Li诱导作用的可能分子机制此外，我们将研究Li是否影响CNS中另一种胶质细胞和星形胶质细胞前体寡树突细胞的生长。我们的初步数据表明，锂增加寡树突细胞增殖。这些机制可能为改善严重神经精神疾病的长期治疗提供了潜在的靶点。