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饮酒倾向和酒精摄入以亚核特异性方式改变终纹床核中降钙素基因相关肽、神经肽Y和小胶质细胞的表达。

Predisposition to Alcohol Drinking and Alcohol Consumption Alter Expression of Calcitonin Gene-Related Peptide, Neuropeptide Y, and Microglia in Bed Nucleus of Stria Terminalis in a Subnucleus-Specific Manner.

作者信息

Rossetti Ilaria, Zambusi Laura, Maccioni Paola, Sau Roberta, Provini Luciano, Castelli M Paola, Gonciarz Krzysztof, Colombo Giancarlo, Morara Stefano

机构信息

Institute of Neuroscience, National Research Council of Italy, Milan, Italy.

Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy.

出版信息

Front Cell Neurosci. 2019 Apr 30;13:158. doi: 10.3389/fncel.2019.00158. eCollection 2019.

DOI:10.3389/fncel.2019.00158
PMID:31114482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6502997/
Abstract

Excessive alcohol consumption is often linked to anxiety states and has a major relay center in the anterior part of bed nucleus of stria terminalis (BNST). We analyzed the impact of (i) genetic predisposition to high alcohol preference and consumption, and (ii) alcohol intake on anterior BNST, namely anterolateral (AL), anteromedial (AM), and anteroventral (lateral + medial subdivisions: AVl, AVm) subnuclei. We used two rat lines selectively bred for low- and high-alcohol preference and consumption, named Sardinian alcohol-non preferring (sNP) and -preferring (sP), respectively, the latter showing also inherent anxiety-related behaviors. We analyzed the modulation of calcitonin gene-related peptide (CGRP; exerting anxiogenic effects in BNST), neuropeptide Y (NPY; exerting mainly anxiolytic effects), and microglia activation (neuroinflammation marker, thought to increase anxiety). Calcitonin gene-related peptide-immunofluorescent fibers/terminals did not differ between alcohol-naive sP and sNP rats. Fiber/terminal NPY-immunofluorescent intensity was lower in BNST-AM and BNST-AVm of alcohol-naive sP rats. Activation of microglia (revealed by morphological analysis) was decreased in BNST-AM and increased in BNST-AVm of alcohol-naive sP rats. Prolonged (30 consecutive days), voluntary alcohol intake under the homecage 2-bottle "alcohol vs. water" regimen strongly increased CGRP intensity in BNST of sP rats in a subnucleus-specific manner: in BNST-AL, BNST-AVm, and BNST-AM. CGRP area sum, however, decreased in BNST-AM, without changes in other subnuclei. Alcohol consumption increased NPY expression, in a subnucleus-specific manner, in BNST-AL, BNST-AVl, and BNST-AVm. Alcohol consumption increased many size/shapes parameters in microglial cells, indicative of microglia de-activation. Finally, microglia density was increased in ventral anterior BNST (BNST-AVl, BNST-AVm) by alcohol consumption. In conclusion, genetic predisposition of sP rats to high alcohol intake could be in part mediated by anterior BNST subnuclei showing lower NPY expression and differential microglia activation. Alcohol intake in sP rats produced complex subnucleus-specific changes in BNST, affecting CGRP/NPY expression and microglia and leading to hypothesize that these changes might contribute to the anxiolytic effects of voluntarily consumed alcohol repeatedly observed in sP rats.

摘要

过量饮酒常与焦虑状态有关，且在终纹床核（BNST）前部有一个主要中继中心。我们分析了（i）高酒精偏好和消费的遗传易感性，以及（ii）酒精摄入对BNST前部，即前外侧（AL）、前内侧（AM）和前腹侧（外侧+内侧亚区：AVl、AVm）亚核的影响。我们使用了两种分别为低酒精偏好和高酒精偏好及消费而选择性培育的大鼠品系，分别命名为撒丁岛非酒精偏好（sNP）和酒精偏好（sP）品系，后者还表现出与焦虑相关的固有行为。我们分析了降钙素基因相关肽（CGRP；在BNST中发挥致焦虑作用）、神经肽Y（NPY；主要发挥抗焦虑作用）的调节以及小胶质细胞激活（神经炎症标志物，被认为会增加焦虑）。未接触酒精的sP和sNP大鼠之间，降钙素基因相关肽免疫荧光纤维/终末无差异。未接触酒精的sP大鼠的BNST-AM和BNST-AVm中，纤维/终末NPY免疫荧光强度较低。通过形态学分析显示，未接触酒精的sP大鼠的BNST-AM中小胶质细胞激活减少，而BNST-AVm中小胶质细胞激活增加。在笼内2瓶“酒精对水”方案下，连续30天自愿饮酒，以亚核特异性方式强烈增加了sP大鼠BNST中CGRP强度：在BNST-AL、BNST-AVm和BNST-AM中。然而，BNST-AM中CGRP面积总和减少，其他亚核无变化。酒精消费以亚核特异性方式增加了BNST-AL、BNST-AVl和BNST-AVm中NPY的表达。酒精消费增加了小胶质细胞的许多大小/形状参数，表明小胶质细胞去激活。最后，酒精消费使腹侧前BNST（BNST-AVl、BNST-AVm）中小胶质细胞密度增加。总之，sP大鼠对高酒精摄入的遗传易感性可能部分由BNST前部亚核介导，这些亚核显示较低的NPY表达和不同的小胶质细胞激活。sP大鼠的酒精摄入在BNST中产生了复杂的亚核特异性变化，影响CGRP/NPY表达和小胶质细胞，从而推测这些变化可能有助于解释在sP大鼠中反复观察到的自愿饮用酒精的抗焦虑作用。

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