PRENATAL EXPOSURE TO ETHANOL STIMULATES HYPOTHALAMIC CCR2 CHEMOKINE RECEPTOR SYSTEM: POSSIBLE RELATION TO INCREASED DENSITY OF OREXIGENIC PEPTIDE NEURONS AND ETHANOL DRINKING IN ADOLESCENT OFFSPRING
PRENATAL EXPOSURE TO ETHANOL STIMULATES HYPOTHALAMIC CCR2 CHEMOKINE RECEPTOR SYSTEM: POSSIBLE RELATION TO INCREASED DENSITY OF OREXIGENIC PEPTIDE NEURONS AND ETHANOL DRINKING IN ADOLESCENT OFFSPRING
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DOI：
10.1016/j.neuroscience.2015.09.020
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发表时间：
2015-12-03
期刊：
影响因子：
3.3
通讯作者：
Leibowitz, S. F.
中科院分区：
文献类型：
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作者：
Chang, G. -Q.;Karatayev, O.;Leibowitz, S. F.
临床和动物研究表明，母亲在怀孕期间饮用乙醇会增加后代的饮酒量。可能的潜在机制可能涉及食欲肽，这是刺激产前乙醇暴露和本身促进饮酒。建立在证据表明，乙醇刺激神经免疫因子，如趋化因子CCL 2，在成年大鼠中被证明与食欲肽，黑色素浓集激素（MCH）在外侧下丘脑（LH）共定位，本研究试图调查的可能性，CCL 2或其受体CCR 2在LH刺激产前乙醇暴露，也许特别是在MCH神经元。我们的范例口服乙醇给孕鼠，在低至中等剂量（1或3克/公斤/天）在高峰期下丘脑神经发生，导致在青春期男性后代的两倍增加饮用和偏好乙醇和恢复乙醇饮用的两瓶选择范例下的间歇性访问时间表。产前乙醇暴露的这种影响与青春期前后代LH中MCH表达和MCH+神经元密度增加有关。而在这个年龄段的CCL 2（+）细胞密度低，不受乙醇的影响，CCR 2（+）细胞在LH中密集，产前乙醇增加，大部分（83-87%）被鉴定为神经元，并发现共定位MCH。产前乙醇还刺激了胚胎中CCR 2（+）和MCH+神经元的发生，它们共同标记了增殖标记物BrdU。乙醇还增加了LH中共表达CCR 2和MCH的神经元的发生和密度，对照大鼠中不存在的三重标记的CCR 2（+）/MCH+/BrdU（+）神经元占乙醇暴露大鼠中新产生的神经元的35%。由于趋化因子和MCH系统都被认为促进乙醇消耗，青春期前大鼠LH中CCR 2（+）/MCH+神经元的密度更大，这表明这些系统共同作用促进青春期饮酒。(C)2015年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Clinical and animal studies indicate that maternal consumption of ethanol during pregnancy increases alcohol drinking in the offspring. Possible underlying mechanisms may involve orexigenic peptides, which are stimulated by prenatal ethanol exposure and themselves promote drinking. Building on evidence that ethanol stimulates neuroimmune factors such as the chemokine CCL2 that in adult rats is shown to colocalize with the orexigenic peptide, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), the present study sought to investigate the possibility that CCL2 or its receptor CCR2 in LH is stimulated by prenatal ethanol exposure, perhaps specifically within MCH neurons. Our paradigm of intraoral administration of ethanol to pregnant rats, at low-to-moderate doses (1 or 3 g/kg/day) during peak hypothalamic neurogenesis, caused in adolescent male offspring twofold increase in drinking of and preference for ethanol and reinstatement of ethanol drinking in a two-bottle choice paradigm under an intermittent access schedule. This effect of prenatal ethanol exposure was associated with an increased expression of MCH and density of MCH+ neurons in LH of preadolescent offspring. Whereas CCL2(+) cells at this age were low in density and unaffected by ethanol, CCR2(+) cells were dense in LH and increased by prenatal ethanol, with a large percentage (83-87%) identified as neurons and found to colocalize MCH. Prenatal ethanol also stimulated the genesis of CCR2(+) and MCH+ neurons in the embryo, which co-labeled the proliferation marker, BrdU. Ethanol also increased the genesis and density of neurons that co-expressed CCR2 and MCH in LH, with triple-labeled CCR2(+)/MCH+/BrdU(+) neurons that were absent in control rats accounting for 35% of newly generated neurons in ethanol-exposed rats. With both the chemokine and MCH systems believed to promote ethanol consumption, this greater density of CCR2(+)/MCH+ neurons in the LH of preadolescent rats suggests that these systems function together in promoting alcohol drinking during adolescence. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.