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リエゾンラボ研究会
発表内容

Title:

Regulation of hippocampal neurons by antidepressant stimulation and exploration for factors contributing to antidepressant effects

 

Speaker:

Eri Segi-Nishida (Department of Biological Science and Technology, Tokyo University of Science)

 

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

  1. Segi-Nishida E, Warner-Schmidt JL, Duman RS: Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus. Proc. Natl. Acad. Sci. USA 105: 11352-11357, 2008.
  2. Imoto Y., Kira T., Sukeno M., Nishitani N., Nagayasu K., Nakagawa T., Kaneko S., Kobayashi K., Segi-Nishida E: Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic activity and granule cell dematuration in the dentate gyrus. Mol Brain, 8:29, 2015.
  3. Imoto Y., Segi-Nishida E, Suzuki H., Kobayashi K: Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment. Mol Brain, 10:8, 2017
  4. Ueno M, Sugimoto M, Ohtsubo K, Sakai N, Endoh A, Shikano K, Imoto Y, Segi-Nishida E. The effect of electroconvulsive seizure on survival, neuronal differentiation, and expression of the maturation marker in the adult mouse hippocampus. J Neurochem. 149(4):488-498. 2019.
  5. Kobayashi Y, Segi-Nishida E. Search for factors contributing to resistance to the electroconvulsive seizure treatment model using adrenocorticotrophic hormone-treated mice. Pharmacol Biochem Behav. 186:172767. 2019.
  6. Yoshioka T, Yamada D, Kobayashi R, Segi-Nishida E, Saitoh A. Chronic vicarious social defeat stress attenuates new-born neuronal cell survival in mouse hippocampus. Behav Brain Res. 2022;416:113536.