Neuromodulatory effect of interleukin 1β in the dorsal raphe nucleus on individual differences in aggression.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
26
06
2020
accepted:
09
04
2021
revised:
26
03
2021
pubmed:
2
5
2021
medline:
31
5
2022
entrez:
1
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33931727
doi: 10.1038/s41380-021-01110-4
pii: 10.1038/s41380-021-01110-4
pmc: PMC8556414
mid: NIHMS1739111
doi:
Substances chimiques
IL1B protein, mouse
0
Interleukin-1beta
0
Serotonin
333DO1RDJY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2563-2579Subventions
Organisme : NIMH NIH HHS
ID : R01 MH104559
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH127820
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH114882
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090264
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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