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.
