Neuromodulatory effect of interleukin 1β in the dorsal raphe nucleus on individual differences in aggression.

Autor: Takahashi A; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Ibaraki, Japan.; Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA., Aleyasin H; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Stavarache MA; Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, USA., Li L; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Cathomas F; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Parise LF; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Lin HY; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Burnett CJ; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Aubry A; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Flanigan ME; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Brancato A; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties of Excellence 'G. D'Alessandro', University of Palermo, Palermo, Italy., Menard C; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval and CERVO Brain Research Center, Quebec City, QC, Canada., Pfau ML; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Kana V; Department of Oncological Sciences, Tisch Cancer Institute and Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Wang J; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Hodes GE; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; School of Neuroscience, Virginia Tech, Blacksburg, VA, USA., Sasaki T; Department of Anatomy and Neuroscience, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan., Kaplitt MG; Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, USA., Ogawa S; Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Ibaraki, Japan., McEwen BS; Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA., Russo SJ; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. scott.russo@mssm.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2022 May; Vol. 27 (5), pp. 2563-2579. Date of Electronic Publication: 2021 Apr 30.
DOI: 10.1038/s41380-021-01110-4
Abstrakt: Heightened aggressive behavior is considered as one of the central symptoms of many neuropsychiatric disorders including autism, schizophrenia, and dementia. The consequences of aggression pose a heavy burden on patients and their families and clinicians. Unfortunately, we have limited treatment options for aggression and lack mechanistic insight into the causes of aggression needed to inform new efforts in drug discovery and development. Levels of proinflammatory cytokines in the periphery or cerebrospinal fluid were previously reported to correlate with aggressive traits in humans. However, it is still unknown whether cytokines affect brain circuits to modulate aggression. Here, we examined the functional role of interleukin 1β (IL-1β) in mediating individual differences in aggression using a resident-intruder mouse model. We found that nonaggressive mice exhibit higher levels of IL-1β in the dorsal raphe nucleus (DRN), the major source of forebrain serotonin (5-HT), compared to aggressive mice. We then examined the effect of pharmacological antagonism and viral-mediated gene knockdown of the receptors for IL-1 within the DRN and found that both treatments consistently increased aggressive behavior of male mice. Aggressive mice also exhibited higher c-Fos expression in 5-HT neurons in the DRN compared to nonaggressive mice. In line with these findings, deletion of IL-1 receptor in the DRN enhanced c-Fos expression in 5-HT neurons during aggressive encounters, suggesting that modulation of 5-HT neuronal activity by IL-1β signaling in the DRN controls expression of aggressive behavior.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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