Pituitary Adenylate Cyclase-Activating Polypeptide-27 (PACAP-27) in the Thalamic Paraventricular Nucleus Is Stimulated by Ethanol Drinking.
Pituitary Adenylate Cyclase-Activating Polypeptide-27 (PACAP-27) in the Thalamic Paraventricular Nucleus Is Stimulated by Ethanol Drinking.
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DOI：
10.1111/acer.13826
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Barson JR
中科院分区：
文献类型：
--
作者：
Gupta A;Gargiulo AT;Curtis GR;Badve PS;Pandey S;Barson JR
丘脑室旁核（PVT）是一种影响饮酒的边缘脑结构，但该核中转录的可能参与这种行为的神经化学物质尚未得到充分表征。已知神经肽垂体腺苷酸环化酶激活多肽（PACAP）在其他边缘系统区域转录，并参与许多与PVT本身相同的行为，可能包括饮酒。它以两种亚型存在，PACAP-38和PACAP-27，前者在大多数大脑区域中表达水平较高。本研究的目的是表征PVT中的PACAP，并评估其对乙醇饮用的反应。首先，使用定量实时PCR和免疫组织化学检查未接触乙醇的Sprague-Dawley大鼠，以表征贯穿PVT的喙尾轴的PACAP mRNA和肽。接下来，使用免疫组织化学检查未接触乙醇的vGLUT 2-GFP转基因小鼠，以鉴定PVT中PACAPergic细胞的神经化学表型。最后，Long-Evans大鼠在无意识进入模式下饮用20%乙醇，然后用定量实时PCR和免疫组织化学检测乙醇对PVT中内源性PACAP的影响。在这个核的后部比前部更致密。蛋白质亚型PACAP-27在PVT中的细胞体中占很高的百分比，特别是在后部，而PACAP-38则在纤维中致密。所有PACAP-27+细胞均与谷氨酸共标记，谷氨酸本身在大多数PVT细胞中被鉴定。乙醇饮用导致增加PACAP基因的表达和PACAP-27的水平在个别细胞的PVT。本研究的特点PVT神经肽，PACAP，其未充分研究的蛋白质亚型，PACAP-27，并表明，它是参与药理学相关的乙醇饮用。这表明，PACAP-27应进一步研究其在乙醇饮用中的可能作用。
The paraventricular nucleus of the thalamus (PVT) is a limbic brain structure that affects ethanol drinking, but the neurochemicals transcribed in this nucleus that may participate in this behavior have yet to be fully characterized. The neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), is known to be transcribed in other limbic areas and to be involved in many of the same behaviors as the PVT itself, possibly including ethanol drinking. It exists in two isoforms, PACAP-38 and PACAP-27, with the former expressed at higher levels in most brain regions. The purpose of this study was to characterize PACAP in the PVT and to assess its response to ethanol drinking. First, ethanol-naïve, Sprague-Dawley rats were examined using quantitative real-time PCR and immunohistochemistry, to characterize PACAP mRNA and peptide throughout the rostro-caudal axis of the PVT. Next, ethanol-naïve, vGLUT2-GFP transgenic mice were examined using immunohistochemistry, to identify the neurochemical phenotype of the PACAPergic cells in the PVT. Finally, Long-Evans rats were trained to drink 20% ethanol under the intermittent-access paradigm and then examined with quantitative real-time PCR and immunohistochemistry, to determine the effects of ethanol on endogenous PACAP in the PVT. Gene expression of PACAP was detected across the entire PVT, denser in the posterior than the anterior portion of this nucleus. The protein isoform, PACAP-27, was present in a high percentage of cell bodies in the PVT, again particularly in the posterior portion, while PACAP-38 was instead dense in fibers. All PACAP-27+ cells co-labeled with glutamate, which itself was identified in the majority of PVT cells. Ethanol drinking led to an increase in PACAP gene expression and in levels of PACAP-27 in individual cells of the PVT. The present study characterizes the PVT neuropeptide, PACAP, and its understudied protein isoform, PACAP-27, and demonstrates that it is involved in pharmacologically-relevant ethanol drinking. This indicates that PACAP-27 should be further investigated for its possible role in ethanol drinking.
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