Frontiers in Cellular Neuroscience ( IF 4.2 ) Pub Date : 2020-08-24 , DOI: 10.3389/fncel.2020.580583 Kathryn M. Harper , Darin J. Knapp , Caroline A. Todd , Irina Balan , Laure Aurelian , Hugh E. Criswell , George R. Breese
Chemokines such as chemokine (C-C motif) ligand 2 (CCL2) play a role in several behaviors, including anxiety-like behavior, but whether neurons are an important source of CCL2 for behavior and how neuronal CCL2 may work to affect behavior are still debated. When a herpes simplex virus (HSV) vector was used to knockdown CCL2 mRNA in neurons of the central nucleus of the amygdala (CeA) in rats experiencing multiple withdrawals from low dose ethanol, anxiety-like behavior appeared in the social interaction task. To examine this finding further Fractalkine (CX3CL1), a chemokine that is often found to have an opposing function to CCL2 was measured in these rats. Both alcohol withdrawal and CCL2 knockdown increased the levels of the anti-inflammatory protein CX3CL1. The combination of alcohol withdrawal and CCL2 knockdown decreased CX3CL1 and may alter pro-inflammatory/anti-inflammatory balance, and thus highlights the potential importance of CCL2 and CCL2/CX3CL1 balance in anxiety. To find a mechanism by which neuronal chemokines like CCL2 could affect behavior, retrograde tracing with fluorescent nanobeads was done in two brain regions associated with anxiety the bed nucleus of the stria terminalis (BNST) and the ventral periaqueductal gray (VPAG). These studies identified CeA projection neurons to these brain regions that contain CCL2. To demonstrate that CCL2 can be transported
中文翻译:
含中枢杏仁核神经元控制酒精戒断诱发焦虑的表型CCL2。
趋化因子(例如趋化因子(CC基序)配体2(CCL2))在多种行为(包括类似焦虑的行为)中起作用,但是神经元是否是行为的重要CCL2来源以及神经元CCL2可能如何影响行为。当使用单纯疱疹病毒(HSV)载体敲低遭受多次低剂量乙醇戒断的大鼠杏仁核(CeA)中枢神经元神经元中的CCL2 mRNA时,社交互动任务中出现了类似焦虑的行为。为了进一步检查这一发现,在这些大鼠中测量了常被发现与CCL2具有相反功能的趋化因子Fractalkine(CX3CL1)。戒酒和敲除CCL2均可增加抗炎蛋白CX3CL1的水平。戒酒和CCL2降低的组合降低了CX3CL1,并可能改变促炎/抗炎平衡,因此突出了CCL2和CCL2 / CX3CL1平衡在焦虑中的潜在重要性。为了找到像CCL2这样的神经元趋化因子影响行为的机制,在与焦虑相关的终末床床核(BNST)和腹周导水管灰色(VPAG)的两个大脑区域中进行了荧光纳米珠的逆行追踪。这些研究确定了CeA投射神经元到包含CCL2的这些大脑区域。演示可以运输CCL2 在两个与焦虑相关的大脑区域进行了荧光纳米珠的逆行示踪,该区域与纹状体终末床核(BNST)和腹周导水管灰色(VPAG)有关。这些研究确定了CeA投射神经元到包含CCL2的这些大脑区域。演示可以运输CCL2 在两个与焦虑相关的大脑区域进行了荧光纳米珠的逆行示踪,该区域与纹状体终末床核(BNST)和腹周导水管灰色(VPAG)有关。这些研究确定了CeA投射神经元到包含CCL2的这些大脑区域。演示可以运输CCL2