THE STUDY OF THE THERAPEUTIC MECHANISMS OF ANTIDEPRESSANT ON NEURONAL REMODELING

我们利用差异克隆技术从大鼠额叶皮层和下丘脑中鉴定出200个抗抑郁相关基因（ADRG）。在本研究中，我们继续在大鼠海马中进行筛选，共鉴定了707个cDNA，并开发了ADRG芯片。最近，我们使用ADRG微阵列来寻找慢性抗抑郁药物治疗和重复ECT后常见的5个基因。电痉挛疗法是另一种广泛应用于抑郁症患者的治疗方法，尤其是对抗抑郁药物有抗药性的患者。有趣的是，我们发现一些与神经突生长相关的基因在慢性抗抑郁药物治疗和反复电痉挛治疗后通常会被诱导或减少。因此，未知的候选ADRG基因可能属于与神经突生长相关的功能。将adrg# 102和adrg# 123亚克隆到GFP表达载体上，转染到ngf诱导的分化PC12细胞中。形态学变化的测量表明，转染后的细胞中最长的神经突的平均长度和每个细胞的神经突的总长度分别显著缩短。此外，每个细胞的平均神经突数在转染后也显著减少。抗抑郁药的长期治疗作用之一可能与功能和结构神经可塑性的改变有关。

We have previously identified 200 cDNA fragments as antidepressant related genes (ADRG) from rat frontal cortex and hypothalamus using differential cloning technique. In the present study, we continued this screening in rat hippocampus and identified total of 707 cDNA and developed the ADRG microarray. More recently, we used ADRG microarray to search for s**e genes commonly induced after chronic antidepressant treatment and repeated ECT. ECT is another therapy for depressive patients that is widely used, particularly in the treatment of patients who are resistant to antidepressant medications. Interestingly, we found some genes related to neurite outgrowth, were commonly induced or decreased after chronic antidepressant treatment and repeated ECT. Thus, the unknown candidate ADRG genes may be thought that belong to the function related to the neurite outgrowth. ADRG#102 and ADRG#123 were subcloned to GFP expression vector and transfected to NGF-induced differentiated PC12 cels. Measurement of the morphological changes demonstrated that the mean length of the longest neurite in each cell and the total length of neurites per cell was significantly shorter in the transfectants, respectively. In addition, the mean neurite number per cell was also significantly smaller in the transfectants. One of the long-term therapeutic action of antidepressant may be related to the changes of both functional and structural neuroplasticity.