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Department of Chemitry

International Journal

Molecular Psychiatry
년도 2019
학술지명 Molecular Psychiatry
논문명 Hippocampal mossy cell involvement in neurogenic and behavioral responses to chronic antidepressant treatment
게재권/집
수록페이지
저자명 Oh SJ, Cheng J, Jang JH, Arace J, Jeong MS, Shin CH, Park JR, Jin JH, Greengard P, and Oh YS
Link 관련링크 https://www.nature.com/articles/s41380-019-0384-6 6332회 연결
Oh SJ, Cheng J, Jang JH, Arace J, Jeong MS, Shin CH, Park JR, Jin JH, Greengard P, and Oh YS (2019) Hippocampal mossy cell involvement in neurogenic and behavioral responses to chronic antidepressant treatment. Molecular Psychiatry. 2019 Mar 5. Doi: 10.1038/s41380-019-0384-6.


Abstract

Most antidepressants, including selective serotonin reuptake inhibitors (SSRIs), initiate their drug actions by rapid elevation of serotonin, but they take several weeks to achieve therapeutic onset. This therapeutic delay suggests slow adaptive changes in multiple neuronal subtypes and their neural circuits over prolonged periods of drug treatment. Mossy cells are excitatory neurons in the dentate hilus that regulate dentate gyrus activity and function. Here we show that neuronal activity of hippocampal mossy cells is enhanced by chronic, but not acute, SSRI administration. Behavioral and neurogenic effects of chronic treatment with the SSRI, fluoxetine, are abolished by mossy cell-specific knockout of p11 or Smarca3 or by an inhibition of the p11/AnxA2/SMARCA3 heterohexamer, an SSRI-inducible protein complex. Furthermore, simple chemogenetic activation of mossy cells using Gq-DREADD is sufficient to elevate the proliferation and survival of the neural stem cells. Conversely, acute chemogenetic inhibition of mossy cells using Gi-DREADD impairs behavioral and neurogenic responses to chronic administration of SSRI. The present data establish that mossy cells play a crucial role in mediating the effects of chronic antidepressant medication. Our results indicate that compounds that target mossy cell activity would be attractive candidates for the development of new antidepressant medications.