Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation
Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation
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DOI：
10.1016/j.tox.2014.12.009
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发表时间：
2015-02-03
期刊：
影响因子：
4.5
通讯作者：
Shibutani, Makoto
中科院分区：
文献类型：
--
作者：
Itahashi, Megu;Abe, Hajime;Shibutani, Makoto
已知六氯酚(HCP)可引起动物中枢和外周神经系统髓鞘内神经纤维的空泡化。本研究通过在妊娠第6天至产后第21天的饮食中添加0(对照组)、100或300ppm的HCP，研究了母亲暴露于HCP对大鼠子代海马神经发生的影响。出生后第21天，雌性仔鼠海马亚颗粒下带(SGZ)T盒2(+)祖细胞和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记(+)凋亡细胞数量减少，并伴有髓鞘空泡化和海马伞神经纤维微管蛋白β3链点状染色。此外，海马齿状回胆碱能受体、烟碱β2和B细胞CLL/淋巴瘤2(Bcl2)的转录水平降低。HCP暴露不改变PND 21和PND 77齿状门区SGZ增殖细胞数和表达γ-氨基丁酸(GABA)能中间神经元亚群。尽管仍有部分髓鞘空泡化，但在PND 21暴露的子代中观察到的所有其他变化在PND 77时消失。这些结果表明，在300ppm的HCP水平下，母亲暴露于HCP可通过线粒体凋亡途径可逆地减少子代海马神经发生中的2b型中期祖细胞。神经发生可能受到颗粒细胞系和/或GABA能中间神经元的胆碱能输入功能障碍的影响，如隔-海马区髓鞘空泡化引起的chrnb2(+)转录水平下降和chrnb(2+)中间神经元数量减少所表明的。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2(+) progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling(+) apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing gamma-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction of cholinergic inputs into granule cell lineages and/or GABAergic interneurons as indicated by decreased transcript levels of Chrnb2(+) and numbers of Chrnb(2+) interneurons caused by myelin vacuolation in the septal-hippocampal pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.