APOPTOSIS (PROGRAMMED CELL DEATH) IN PSYCHIATRIC DISORDERS

这个项目的目标是确定程序性细胞死亡 细胞凋亡（apoptosis）与精神疾病有关， 精神分裂症，躁郁症，母亲剥夺和癫痫。 初步 数据显示，ApopTag标记的凋亡细胞的数量是 在12日龄大鼠的母体剥夺后， 杏仁核点燃癫痫发作后， 在两种动物模型中，凋亡阳性细胞的数量是不同的。 母源剥夺组阳性细胞分布于各处 （大脑皮层、白色物质[胼胝体、终纹和 内囊]、丘脑等），而阳性细胞在 杏仁核点燃癫痫发作主要是海马内的中间神经元 阵 阳性细胞的形态与对照组相似。 在两种模型中增加bax（细胞自杀基因）mRNA表达。 因此，未来的研究将集中在糖尿病相关基因， 如Bax，以确定它们是否在凋亡过程中发挥作用。 实验计划将Bax cDNA亚克隆到腺相关病毒中 载体与LacZ（蓝色标记基因）形成融合蛋白，然后 转移到培养的细胞系中，以直接确定是否过度 bax的表达可诱导细胞凋亡。 细胞凋亡可能是精神疾病的普遍现象， 精神分裂症和躁郁症 死后人脑切片 来自精神分裂症和双相情感障碍患者（可在 1996年夏天从NAMI脑库）将与ApopTag研究 加上原位凋亡检测技术。

The goal of this project is to determine whether programmed cell death (apoptosis) is involved in the psychiatric disorders such as schizophrenia, bipolar, maternal deprivation, and seizures. Preliminary data have shown that the number of ApopTag-labeled apoptosis cells were both increased in the brain after maternal deprivation of 12 day-old rats and after amygdala-kindled seizures in adult rats, but the distribution of the apoptosis-positive cells was different in these two animal models. The positive cells in maternal deprivation were distributed everywhere (cerebral cortex, white matter [corpus callosum, stria terminalis, and internal capsule], thalamus, etc.), while the positive cells in the amygdala-kindled seizures were mainly interneurons in the hippocampus formation. The patterns of apoptosis-positive cells were similar to the increased bax (a cell suicide gene) mRNA expression in both models. Therefore, future studies will focus on the apoptosis-related genes such as Bax, to determine if they play a role in the apoptosis process. Experiments are planned to subclone Bax cDNA into adeno-associated virus vector to form a fusion protein with LacZ (a blue marker gene), and then transfer into cultured cell lines to determine directly if the over expression of bax can induce apoptosis. Apoptosis may be a general phenomenon in the psychiatric disorders such as schizophrenia and bipolar disorders. Postmortem human brain slices from patients with schizophrenia and bipolar disorders (available in summer of 1996 from the NAMI Brain Bank) will be studied with the ApopTag plus in situ apoptosis detection techniques.