Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.
Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.
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DOI：
10.3390/brainsci6030025
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发表时间：
2016-07-27
期刊：
影响因子：
3.3
通讯作者：
Breese GR
中科院分区：
文献类型：
--
作者：
Knapp DJ;Harper KM;Whitman BA;Zimomra Z;Breese GR
压力是酒精复发的一个强有力的危险因素，可能会产生类似慢性酒精暴露对神经生物学系统的影响。随着神经免疫系统成为一个突出的重点，在研究的神经生物学后果的压力，以及慢性酒精暴露被证明是一个有价值的焦点，在这方面，本研究试图比较的影响，压力和慢性酒精暴露的诱导成分的神经免疫系统。将大鼠暴露于1小时的轻度应激源（约束）或暴露于从15天的慢性酒精暴露中戒断（即，从慢性乙醇中戒断，WCE）并评估脑中的神经免疫mRNA。单独的束缚应激在4 h内升高了大脑皮质中的趋化因子（C-C基序）配体2（CCL 2）、白细胞介素-1-β（IL-1β）、肿瘤坏死因子α（TNFα）和toll样受体4（TLR 4）mRNA，并在24 h时恢复至对照水平。这些增加并不伴随着相应蛋白质的增加。退出WCE也会增加细胞因子，但在不同的细胞因子和大脑区域中的程度不同。在皮质中，应激和WCE诱导CCL 2、TNFα、IL-1β和TLR 4 mRNA。在下丘脑中，仅WCE诱导细胞因子（CCL 2和IL-1β），而在海马中，WCE强烈诱导CCL 2，而应激和WCE诱导IL-1β。在杏仁核中，只有WCE诱导CCL 2。最后，基于先前证实的促肾上腺皮质激素释放因子1（CRF 1）受体抑制在阻断WCE诱导的细胞因子mRNA中的作用，将CRF 1受体拮抗剂CP 154，526给予应激大鼠亚组，发现其对CCL 2、TNFα或IL-1β mRNA的诱导无活性。这些差异的结果表明，压力和WCE表现出广泛的神经免疫效应，在大脑中的细胞因子和大脑区域，CRF抑制可能不是一个相关的机制，在非酒精暴露的动物。总的来说，这些作用在其神经免疫靶点和神经解剖学特异性方面是复杂的。进一步研究细胞因子诱导在神经解剖区域的差异分布，单个细胞类型（例如，神经元表型和神经胶质）、慢性酒精暴露的严重程度以及不同的应激类型可能证明有助于理解诱导的差异机制和用于酒精中毒药物干预的靶向选择系统。
Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint) or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE) and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C–C motif) ligand 2 (CCL2), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNFα) and toll-like receptor 4 (TLR4) mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β) while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally—based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1) receptor inhibition in blocking WCE-induced cytokine mRNAs—the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals. Overall, these effects are complex in terms of their neuroimmune targets and neuroanatomical specificity. Further investigation of the differential distribution of cytokine induction across neuroanatomical regions, individual cell types (e.g., neuronal phenotypes and glia), severity of chronic alcohol exposure, as well as across differing stress types may prove useful in understanding differential mechanisms of induction and for targeting select systems for pharmacotherapeutic intervention in alcoholism.
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影响因子：
3.3
作者：
Felger JC;Lotrich FE
通讯作者：
Lotrich FE
DOI：
10.1016/j.pnpbp.2012.11.007
发表时间：
2013-04-05
影响因子：
5.6
作者：
Dodd, Seetal;Maes, Michael;Berk, Michael
通讯作者：
Berk, Michael
影响因子：
3.7
作者：
Girotti, Milena;Donegan, Jennifer J.;Morilak, David A.
通讯作者：
Morilak, David A.
影响因子：
13.5
作者：
Breese, George R.;Sinha, Rajita;Heilig, Markus
通讯作者：
Heilig, Markus
影响因子：
10.6
作者：
Crews, Fulton T.;Qin, Liya;Sheedy, Donna;Vetreno, Ryan P.;Zou, Jian
通讯作者：
Zou, Jian