The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.

Cell
Authors
Keywords
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
Journal
Cell
Volume
173
Issue
5
Pages
1265-1279.e19
Date Published
2018 05 17
ISSN
1097-4172
DOI
10.1016/j.cell.2018.03.037
PubMed ID
29775595
PubMed Central ID
PMC5967263
Links
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