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丘脑室旁核中的垂体腺苷酸环化酶激活多肽(PACAP)细胞:与雄性和雌性小鼠暴饮暴食型进食的关系。

Pituitary adenylate cyclase-activating polypeptide (PACAP) cells in the paraventricular nucleus of the thalamus: relationship with binge-type eating in male and female mice.

作者信息

Curtis Genevieve R, Carpenter Brody A, Pirino Breanne E, Hawks Annie, Li George, Barson Jessica R

机构信息

Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA, 19129, USA.

出版信息

Psychopharmacology (Berl). 2025 Feb;242(2):413-426. doi: 10.1007/s00213-024-06692-9. Epub 2024 Sep 28.

Abstract

RATIONALE

Both the paraventricular nucleus of the thalamus (PVT) and the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), are thought to be involved in food intake. Importantly, PACAP is expressed in cells of the PVT.

OBJECTIVES

To determine if PACAP in cells of the PVT might mediate some of the involvement of the PVT with palatable food intake.

METHODS

In male and female C57BL/6 J mice and PACAP-Cre transgenic mice on a C57BL/6 J background, limited access to Milk Chocolate Ensure Plus® was used to establish a model of binge-type eating. Next, using quantitative real-time PCR, gene expression of PACAP in the PVT was measured in relation to this binge-type eating. Finally, using chemogenetics in PACAP-Cre transgenic mice, the effect of activation of PVT PACAP cells on binge-type eating was determined.

RESULTS

Males and females both engaged in binge-type eating with Ensure, although females engaged in this behavior to a greater degree than males. While females also had a higher baseline level of PVT PACAP mRNA than males, only males showed an increase in levels of PACAP after a history of exposure to Ensure, and only males showed a reduction in levels of PACAP immediately prior to a binge session. Conversely, activation of PACAP cells in the PVT reduced binge-type eating of Ensure, specifically in male mice.

CONCLUSIONS

The present findings indicate that PVT PACAP cells influence and are influenced by binge-type eating. Thus, PACAP in the PVT might mediate some of the known involvement of the PVT with palatable food intake.

摘要

理论依据

丘脑室旁核(PVT)和神经肽垂体腺苷酸环化酶激活多肽(PACAP)均被认为与食物摄入有关。重要的是,PACAP在PVT的细胞中表达。

目的

确定PVT细胞中的PACAP是否可能介导PVT在美味食物摄入中的部分作用。

方法

在雄性和雌性C57BL/6 J小鼠以及C57BL/6 J背景的PACAP-Cre转基因小鼠中,使用有限量的牛奶巧克力安素加强型饮料(Milk Chocolate Ensure Plus®)建立暴饮暴食型饮食模型。接下来,使用定量实时PCR,测量与这种暴饮暴食型饮食相关的PVT中PACAP的基因表达。最后,在PACAP-Cre转基因小鼠中使用化学遗传学方法,确定激活PVT的PACAP细胞对暴饮暴食型饮食的影响。

结果

雄性和雌性小鼠都出现了饮用安素后的暴饮暴食型饮食行为,尽管雌性小鼠的这种行为比雄性更明显。虽然雌性小鼠PVT中PACAP mRNA的基线水平也高于雄性,但只有雄性小鼠在接触安素后PACAP水平升高,且只有雄性小鼠在暴饮暴食前即刻PACAP水平降低。相反,激活PVT中的PACAP细胞可减少饮用安素后的暴饮暴食型饮食行为,特别是在雄性小鼠中。

结论

目前的研究结果表明,PVT的PACAP细胞会影响暴饮暴食型饮食行为,并受其影响。因此,PVT中的PACAP可能介导了PVT在美味食物摄入中已知的部分作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beb1/11774950/6fcbd4560fe7/213_2024_6692_Fig1_HTML.jpg

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