For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

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

TitleNeuromodulatory effect of interleukin 1β in the dorsal raphe nucleus on individual differences in aggression.
Publication TypeJournal Article
Year of Publication2021
AuthorsTakahashi A, Aleyasin H, Stavarache MA, Li L, Cathomas F, Parise LF, Lin H-Y, C Burnett J, Aubry A, Flanigan ME, Brancato A, Menard C, Pfau ML, Kana V, Wang J, Hodes GE, Sasaki T, Kaplitt MG, Ogawa S, McEwen BS, Russo SJ
JournalMol Psychiatry
Date Published2021 Apr 30
ISSN1476-5578
Abstract

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.

DOI10.1038/s41380-021-01110-4
Alternate JournalMol Psychiatry
PubMed ID33931727
Grant ListR01 MH090264-06 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01 MH104559-02 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
JP17H04766 / / MEXT | Japan Society for the Promotion of Science (JSPS) /
JP15K12773 / / MEXT | Japan Society for the Promotion of Science (JSPS) /
JP19H05202 / / MEXT | Japan Society for the Promotion of Science (JSPS) /