The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.
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Abstract | Chronic social isolation causes severe psychological effects in humans, but their neural bases remain poorly understood. 2 weeks (but not 24 hr) of social isolation stress (SIS) caused multiple behavioral changes in mice and induced brain-wide upregulation of the neuropeptide tachykinin 2 (Tac2)/neurokinin B (NkB). Systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic SIS. Conversely, enhancing NkB expression and release phenocopied SIS in group-housed mice, promoting aggression and converting stimulus-locked defensive behaviors to persistent responses. Multiplexed analysis of Tac2/NkB function in multiple brain areas revealed dissociable, region-specific requirements for both the peptide and its receptor in different SIS-induced behavioral changes. Thus, Tac2 coordinates a pleiotropic brain state caused by SIS via a distributed mode of action. These data reveal the profound effects of prolonged social isolation on brain chemistry and function and suggest potential new therapeutic applications for Nk3R antagonists. |
Year of Publication | 2018
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Journal | Cell
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Volume | 173
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Issue | 5
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Pages | 1265-1279.e19
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Date Published | 2018 05 17
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ISSN | 1097-4172
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DOI | 10.1016/j.cell.2018.03.037
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PubMed ID | 29775595
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PubMed Central ID | PMC5967263
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Grant list | K99 MH108734 / MH / NIMH NIH HHS / United States
R01 MH070053 / MH / NIMH NIH HHS / United States
R01 MH085082 / MH / NIMH NIH HHS / United States
R01 MH112593 / MH / NIMH NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States
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