Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat.

Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat.
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DOI:
10.1016/j.neuroscience.2010.06.008
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发表时间:
2010-09-01
期刊:
影响因子:
3.3
通讯作者:
Light, K. E.
Light, K. E.
中科院分区:
医学3区
文献类型:
--
作者:
Pierce, D. R.;Hayar, A.;Williams, D. K.;Light, K. E.

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大鼠出生后4-6天(PN)乙醇暴露改变小脑发育,导致浦肯野细胞显著丢失。然而,对于存活下来的神经元发生了什么,我们知之甚少。在本研究中,在PN 4、PN 4 -6或PN 7 -9通过胃内插管给予大鼠幼仔每日剂量的乙醇(3.6或4.5 g/kg体重)。然后在PN 14上用共聚焦显微镜观察攀缘纤维与浦肯野细胞之间的相互作用。用钙结合蛋白-D28 k(以显示浦肯野细胞)和囊泡谷氨酸转运蛋白2(VGluT 2,以显示攀爬纤维)的抗体对中蚓小脑切片进行染色。从小叶1获得共聚焦z-堆叠图像,并用Imaris软件分析以定量两种抗体的染色。与对照组相比,4.5 g/kg剂量水平的PN 4和PN 4 -6乙醇组中的VGluT 2免疫染色显著降低,表明小脑回路在发育乙醇暴露后显著改变。乙醇暴露后,不仅浦肯野细胞减少,而且存活的神经元中VGluT 2标记的突触也明显减少。突触完整性的这些改变是剂量依赖性和时间依赖性的。
Ethanol exposure during postnatal days (PN) 4-6 in rats alters cerebellar development resulting in significant loss of Purkinje cells. There is little knowledge, however, on what happens to the neurons that survive. In this study, rat pups were treated with a daily dose of ethanol (either 3.6 or 4.5 g/kg body weight) delivered by intragastric intubation on PN4, PN4-6, or PN7-9. Then the interactions between climbing fibers and Purkinje cell were examined on PN14 using confocal microscopy. Mid-vermal cerebellar sections were stained with antibodies to calbindin-D28k (to visualize Purkinje cells) and vesicular glutamate transporter 2 (VGluT2, to visualize climbing fibers). Confocal z-stack images were obtained from Lobule 1 and analyzed with Imaris software to quantify the staining of the two antibodies. The VGluT2 immunostaining was significantly reduced in the PN4 and PN4-6 ethanol groups for the 4.5 g/kg dose level, compared to controls, indicating that the cerebellar circuitry was significantly altered following developmental ethanol exposure. Not only were there fewer Purkinje cells following ethanol exposure, but the surviving neurons had significantly fewer VGluT2-labeled synapses. These alterations in the synaptic integrity were both dose dependent and temporally dependent.
DOI: 10.1002/cne.20354
发表时间: 2004-12-13
影响因子: 2.5
作者:
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期刊: NEUROSCIENCE
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期刊: MOLECULAR BRAIN RESEARCH
影响因子: --
作者:
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