Abstract:

Hippocampal dentate gyrus (DG) has been implicated in the pathophysiological mechanisms of neuropsychiatric disorders including depression and suggested to be an important target for therapeutic treatments. Since approximately one third of patients with depression remain treatment resistant, it is important to know how antidepressants can or cannot induce appropriate responses in the DG. We have demonstrated that different types of antidepressant-like stimulation, such as SSRI and electroconvulsive seizures (ECS), induce similar transcriptional and cellular changes including increased neurogenesis and maturation-related phenotypic transformation in the mouse DG. Gene expression profiling showed that chronic SSRI and repeated ECS induce a similar expression change in the DG. However, which signals are involved in transcriptional changes remains unknown. It is also necessary to address how the transcriptional changes affect those hippocampal functional changew. To address these questions, we focused on the role of transcription factor: serum responsive factor (SRF) in the transcriptional and cellular changes of the DG by ECS, and the contribution of neurotrophin-3 (NT-3), one of the down-regulated genes by antidepressants, in functional changes of the DG. By using adeno associated virus (AAV) expressing targeting gene or artificial microRNA, we found that SRF plays an important role in the responsiveness of the repetitive ECS, and that NT-3 may inhibit early processes in the neurogenesis. In this seminar, we would like to present our research and discuss the response of the hippocampus to stress stimuli.

References:

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