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围产期三丁基锡暴露会影响成年小鼠室旁核下丘脑神经肽 Y 的摄食行为和表达。

Perinatal exposure to tributyltin affects feeding behavior and expression of hypothalamic neuropeptide Y in the paraventricular nucleus of adult mice.

机构信息

Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, Italy.

Department of Neuroscience "Rita Levi-Montalcini", University of Torino, Torino, Italy.

出版信息

J Anat. 2023 Feb;242(2):235-244. doi: 10.1111/joa.13766. Epub 2022 Sep 8.

DOI:10.1111/joa.13766
PMID:36073672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9877477/
Abstract

Organotins such as tributyltin chloride (TBT), are highly diffused environmental pollutants, which act as metabolism disrupting chemicals, i.e. may interfere with fat tissue differentiation, as well as with neuroendocrine circuits, thus impairing the control of energetic balance. We have previously demonstrated that adult exposure to TBT altered the expression of neuropeptides in the hypothalamus. In this study, we orally administered daily a solution containing oil, or TBT (0.25, 2.5, or 25 μg/kg body weight/day) to pregnant females from gestational day 8 until birth, and to their pups from day 0 until post-natal day 21. Our results showed that TBT exposure of female mice during gestation and of pups during lactation permanently altered the feeding efficiency of pups of both sexes and subcutaneous fat distribution in adult males. In addition, the neuropeptide Y system was affected at the level of the paraventricular nucleus, with a decrease in immunoreactivity in both sexes (significant in females for all TBT doses and in males only for intermediate TBT doses), while no effect was observed in other hypothalamic areas (arcuate, ventromedial and dorsomedial nuclei). Metabolic syndrome, as well as obesity and diabetes, which are significant health issues, are considered multifactorial diseases and may be caused by exposure to metabolic disruptors, both in adults and during perinatal life. In addition, our work indicates that TBT doses defined as the tolerably daily intake had a profound and sex-specific long-term effect.

摘要

有机锡化合物,如三丁基锡氯化物(TBT),是高度扩散的环境污染物,作为代谢扰乱化学物质,即可能干扰脂肪组织分化,以及神经内分泌回路,从而损害能量平衡的控制。我们之前已经证明,成年期暴露于 TBT 会改变下丘脑神经肽的表达。在这项研究中,我们从妊娠第 8 天到出生,每天向怀孕的雌性动物口服含有油或 TBT(0.25、2.5 或 25μg/kg 体重/天)的溶液,并向它们的幼仔从出生后第 0 天到第 21 天。我们的结果表明,TBT 在妊娠期间对雌性小鼠和哺乳期对幼仔的暴露会永久性地改变两性幼仔的进食效率和成年雄性的皮下脂肪分布。此外,神经肽 Y 系统在室旁核水平受到影响,两性的免疫反应性降低(所有 TBT 剂量对雌性均显著,仅对中间 TBT 剂量对雄性显著),而其他下丘脑区域(弓状核、腹内侧核和背内侧核)则没有观察到影响。代谢综合征,以及肥胖症和糖尿病,这些都是重大的健康问题,被认为是多因素疾病,可能是由于暴露于代谢扰乱物引起的,无论是在成年期还是在围产期。此外,我们的工作表明,定义为可耐受的每日摄入量的 TBT 剂量具有深远的、性别特异性的长期影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/3b82bb813e13/JOA-242-235-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/a3bc3b77d8ff/JOA-242-235-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/89bac36ad1a7/JOA-242-235-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/c8c593f7010c/JOA-242-235-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/3b82bb813e13/JOA-242-235-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/a3bc3b77d8ff/JOA-242-235-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/89bac36ad1a7/JOA-242-235-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/c8c593f7010c/JOA-242-235-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c9/9877477/3b82bb813e13/JOA-242-235-g005.jpg

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本文引用的文献

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Metabolites. 2021 Jun 9;11(6):368. doi: 10.3390/metabo11060368.
2
Tributyltin Alters Calcium Levels, Mitochondrial Dynamics, and Activates Calpains Within Dorsal Root Ganglion Neurons.三丁基锡改变钙离子水平、线粒体动力学,并激活背根神经节神经元中的钙蛋白酶。
Toxicol Sci. 2021 Apr 12;180(2):342-355. doi: 10.1093/toxsci/kfaa193.
3
Sex differences in behavioral and metabolic effects of gene inactivation: The neuropeptide Y and Y receptors in the brain.
基因失活的行为和代谢效应中的性别差异:大脑中的神经肽Y及其受体
Neurosci Biobehav Rev. 2020 Dec;119:333-347. doi: 10.1016/j.neubiorev.2020.09.020. Epub 2020 Oct 9.
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The impact of endocrine-disrupting chemical exposure in the mammalian hypothalamic-pituitary axis.内分泌干扰化学物质暴露对哺乳动物下丘脑 - 垂体轴的影响。
Mol Cell Endocrinol. 2020 Dec 1;518:110997. doi: 10.1016/j.mce.2020.110997. Epub 2020 Aug 22.
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Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food Intake and Energy Metabolism.代谢干扰化学物质与控制食物摄入和能量代谢的神经内分泌回路改变
Front Endocrinol (Lausanne). 2019 Jan 9;9:766. doi: 10.3389/fendo.2018.00766. eCollection 2018.
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