Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice.
Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice.
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DOI：
10.1016/j.ynstr.2018.01.004
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发表时间：
2018-03
影响因子：
5
通讯作者：
Pryce CR
中科院分区：
文献类型：
--
作者：
Bergamini G;Mechtersheimer J;Azzinnari D;Sigrist H;Buerge M;Dallmann R;Freije R;Kouraki A;Opacka-Juffry J;Seifritz E;Ferger B;Suter T;Pryce CR
心理社会应激是抑郁症的主要危险因素，应激导致外周和中枢免疫激活，免疫激活与多巴胺（DA）神经功能钝化有关，DA功能是奖励兴趣的基础，奖励兴趣降低是抑郁症的核心症状。这些状态在复杂的因果路径中可能是相互独立的。虽然动物模型证据存在于途径中的一些特定步骤中，但目前还没有动物模型证明社会压力导致这些免疫，神经和行为状态中的每一个。这样一个模型将为复杂的途径提供重要的存在证据，并将使因果关系和中介机制的研究在特定的步骤，在途径。因此，在目前的小鼠研究中，我们调查了15天的居民入侵者慢性社会压力（CSS）对这些国家的影响。相对于对照组，CSS小鼠表现出更高的粒细胞，炎性单核细胞和T辅助细胞17的脾脏水平;诱导型一氧化氮合酶的血浆水平;和编码犬尿氨酸途径酶的基因的肝脏表达。CSS在腹侧被盖区导致更高水平的犬尿氨酸和小胶质细胞标记物Iba 1和Cd 11b以及更高的DA D1受体结合活性;在背侧核（NAcc）中导致更高的犬尿氨酸，更低的DA周转率和更低的c-fos表达。DA再摄取抑制剂的药理学挑战确定衰减的DA对CSS小鼠的自发活动和NAcc c-fos表达的刺激作用。在蔗糖奖励的操作性反应的行为测试中，CSS小鼠表现出较少的奖励导向行为，该测试被验证为NAcc DA功能的敏感测定。因此，这项小鼠研究表明，慢性社会应激源导致免疫，神经和行为状态的变化，这些状态被认为是压力和DA依赖性奖励处理中断之间的中介。该模型现在可以应用于调查因果关系，如果证明，在这个免疫神经行为途径的具体步骤的潜在机制，从而确定潜在的治疗靶点。小鼠慢性社会应激（CSS）导致脾和肝免疫激活。小鼠CSS导致中脑边缘免疫激活和多巴胺功能减弱。在操作性测试中，鼠标CSS导致奖励导向行为减少。这构成了研究病理生理机制的重要模型。
Psychosocial stress is a major risk factor for depression, stress leads to peripheral and central immune activation, immune activation is associated with blunted dopamine (DA) neural function, DA function underlies reward interest, and reduced reward interest is a core symptom of depression. These states might be inter-independent in a complex causal pathway. Whilst animal-model evidence exists for some specific steps in the pathway, there is currently no animal model in which it has been demonstrated that social stress leads to each of these immune, neural and behavioural states. Such a model would provide important existential evidence for the complex pathway and would enable the study of causality and mediating mechanisms at specific steps in the pathway. Therefore, in the present mouse study we investigated for effects of 15-day resident-intruder chronic social stress (CSS) on each of these states. Relative to controls, CSS mice exhibited higher spleen levels of granulocytes, inflammatory monocytes and T helper 17 cells; plasma levels of inducible nitric oxide synthase; and liver expression of genes encoding kynurenine pathway enzymes. CSS led in the ventral tegmental area to higher levels of kynurenine and the microglia markers Iba1 and Cd11b and higher binding activity of DA D1 receptor; and in the nucleus accumbens (NAcc) to higher kynurenine, lower DA turnover and lower c-fos expression. Pharmacological challenge with DA reuptake inhibitor identified attenuation of DA stimulatory effects on locomotor activity and NAcc c-fos expression in CSS mice. In behavioural tests of operant responding for sucrose reward validated as sensitive assays for NAcc DA function, CSS mice exhibited less reward-directed behaviour. Therefore, this mouse study demonstrates that a chronic social stressor leads to changes in each of the immune, neural and behavioural states proposed to mediate between stress and disruption of DA-dependent reward processing. The model can now be applied to investigate causality and, if demonstrated, underlying mechanisms in specific steps of this immune-neural-behavioural pathway, and thereby to identify potential therapeutic targets. Mouse chronic social stress (CSS) leads to spleen and liver immune activation. Mouse CSS leads to mesolimbic immune activation and blunted dopamine function. Mouse CSS leads to reduced reward-directed behaviour in operant tests. This constitutes an important model for the study of pathophysiological mechanisms.
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DOI：
10.1523/jneurosci.1758-09.2009
发表时间：
2009-09-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Covington HE 3rd;Maze I;LaPlant QC;Vialou VF;Ohnishi YN;Berton O;Fass DM;Renthal W;Rush AJ 3rd;Wu EY;Ghose S;Krishnan V;Russo SJ;Tamminga C;Haggarty SJ;Nestler EJ
通讯作者：
Nestler EJ
DOI：
10.1523/jneurosci.3905-08.2009
发表时间：
2009-06-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Abdallah L;Bonasera SJ;Hopf FW;O'Dell L;Giorgetti M;Jongsma M;Carra S;Pierucci M;Di Giovanni G;Esposito E;Parsons LH;Bonci A;Tecott LH
通讯作者：
Tecott LH
影响因子：
5.6
作者：
Bergamini, Giorgio;Cathomas, Flurin;Pryce, Christopher R.
通讯作者：
Pryce, Christopher R.
影响因子：
4.6
作者：
Biesmans S;Meert TF;Bouwknecht JA;Acton PD;Davoodi N;De Haes P;Kuijlaars J;Langlois X;Matthews LJ;Ver Donck L;Hellings N;Nuydens R
通讯作者：
Nuydens R
影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.