The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.
The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.
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DOI：
10.1016/j.cell.2018.03.037
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发表时间：
2018-05-17
期刊：
影响因子：
64.5
通讯作者：
Anderson DJ
中科院分区：
文献类型：
--
作者：
Zelikowsky M;Hui M;Karigo T;Choe A;Yang B;Blanco MR;Beadle K;Gradinaru V;Deverman BE;Anderson DJ
长期的社会孤立会对人类造成严重的心理影响，但人们对其神经基础仍知之甚少。两周(但不是24小时)的社会隔离应激(SIS)导致小鼠多种行为变化，并诱导神经肽Tachykinin 2(Tac2)/Neurokinin B(NKB)在全脑范围内上调。全身应用Nk3R拮抗剂几乎可以阻止慢性SIS的所有行为影响。相反，增强NKB的表达和释放群居小鼠的表型SIS，促进攻击性，并将刺激锁定的防御行为转变为持续性反应。对多个脑区Tac2/NKB功能的多路分析显示，在不同的SIS诱导的行为变化中，对多肽及其受体的可分离的、区域特定的需求。因此，Tac2通过一种分布式的行动模式来协调由SIS引起的多效性大脑状态。这些数据揭示了长期的社会隔离对大脑化学和功能的深刻影响，并提示了Nk3R拮抗剂潜在的新的治疗应用。Tac2神经肽系统通过在多个大脑区域的局部作用来协调慢性社交隔离应激的复杂行为效应，表明Nk3R拮抗剂在管理长期社交隔离时的行为变化方面具有治疗潜力。
Chronic social isolation causes severe psychological effects in humans, but their neural bases remains poorly understood. Two weeks (but not 24 hrs) of social isolation stress (SIS) caused multiple behavioral changes in mice, and induced brain-wide up-regulation 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. The Tac2 neuropeptide system orchestrates the complex behavioral effects of chronic social isolation stress by acting locally in multiple brain regions, suggesting the therapeutic potential of Nk3R antagonists for managing behavioral changes upon prolonged social isolation.
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影响因子：
64.5
作者：
Asahina K;Watanabe K;Duistermars BJ;Hoopfer E;González CR;Eyjólfsdóttir EA;Perona P;Anderson DJ
通讯作者：
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影响因子：
24.8
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通讯作者：
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64.5
作者：
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通讯作者：
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