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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 May 19

PMID 29775595

Citations 124

Authors

Moriel Zelikowsky

May Hui

Tomomi Karigo

Andrea Choe

Bin Yang

Mario R Blanco

Keith Beadle

Viviana Gradinaru

Benjamin E Deverman

David J Anderson

Affiliations

Soon will be listed here.

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.

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