Abstract
Previous studies have indicated that high percentage of recurrent major depression patients have hippocampal atrophy. It could be caused not only by the atrophy of existing neurons but also by a reduction of adult hippocampal neurogenesis in dentate gyrus. Thus, the role of neurogenesis in major depression pathophysiology has raised great interest in recent years. From past experiments in our laboratory using learned helplessness animal model of depression, we had found a reduction in adult neurogenesis in the dorsal hippocampus of rats showing learned helplessness behavior. In order to identify the underlying molecular mechanisms for the reduced neurogenesis in dorsal hippocampus, we conducted DNA microarray analysis in dorsal and ventral dentate gyrus of learned helpless, nonhelpless, and control rats. According to gene ontology analysis, we found differentially expressed genes involved in negative regulation of neuroblast proliferation and neurogenesis in LH dorsal, LH ventral and NoLH ventral DG, whereas the neuroprotection was also found in NoLH ventral DG. The GABA related transmission and receptor activity, channel activity, neurotransmission, and fibroblast growth factor receptor signaling pathway were regulated in LH dorsal DG compared to control. In addition to the genetic study, we also found that the protein expression levels of mature- and pro-BDNF were down-regulated in the dorsal DG of LH rats, which was corresponds well with the reduced neurogenesis. Further investigation of candidate genes, pathways and regulation of neurotrophic factors are valuable for finding the crucial mechanisms involved in depression pathology.