Gene expression profiling of early-activated targets of antidepressants in glia cells

The identification of cell-type-specific and early-activated pharmacological targets of antidepressants might help to implement the search for alternative targets to develop drugs with safer side-effect profiles and faster onset of actions. Glia cells are active partners of neurons and blood vessels in supporting a variety of functions such as synaptic communication and blood-brain barrier permeability. Impaired glia cells (astrocytes and microglia cells) characterize postmortem brains of major depressive disorder patients, suggesting that they might be specifically modulated by pharmacological treatments to reverse disease phenotypes. Here, we have treated rat C6 glioma cells, used as a model of astrocytes, with two different classes of antidepressants (desipramine and fluoxetine) and two drugs without antidepressant properties (haloperidol and diazepam) to compare transcriptomes of glia cells after treatment with antidepressants versus drugs without antidepressant properties. To this aim, we used microarrays to detail the global early-activated cell-type-specific gene expression program and identified multiple classes of genes selectively modulated by antidepressants in astrocytes.鉴定抗抑郁药的细胞类型特异性早期激活药理学靶点，有助于探索新型靶点以开发副作用更安全、起效更快的抗抑郁药物。胶质细胞（glia cells）是神经元与血管的功能性协作伙伴，可支持突触传递、血脑屏障通透性维持等多种生理功能。重度抑郁症（major depressive disorder）患者的死后脑组织中，星形胶质细胞（astrocytes）与小胶质细胞（microglia cells）存在功能受损的特征，这提示可通过药理学手段特异性调控此类胶质细胞以逆转疾病表型。本研究以作为星形胶质细胞模型的大鼠C6胶质瘤细胞为对象，分别使用两类抗抑郁药（地昔帕明（desipramine）与氟西汀（fluoxetine））以及两种无抗抑郁活性的药物（氟哌啶醇（haloperidol）与地西泮（diazepam））进行处理，旨在对比抗抑郁药与非抗抑郁药物处理后胶质细胞的转录组差异。为此，我们通过基因微阵列（microarrays）解析了全局范围的早期激活型细胞类型特异性基因表达程序，并鉴定出多类在星形胶质细胞中被抗抑郁药选择性调控的基因。