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出生后发育期间正常和X射线照射大鼠小脑5-羟色胺1A受体的定量分析

Quantification of 5-hydroxytryptamine1A receptors in the cerebellum of normal and X-irradiated rats during postnatal development.

作者信息

Matthiessen L, Daval G, Bailly Y, Gozlan H, Hamon M, Vergé D

机构信息

Département de Cytologie, CNRS UA 1199, Université Pierre et Marie Curie, Paris, France.

出版信息

Neuroscience. 1992 Nov;51(2):475-85. doi: 10.1016/0306-4522(92)90331-u.

DOI:10.1016/0306-4522(92)90331-u
PMID:1465205
Abstract

5-Hydroxytryptamine1A receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitative autoradiographic studies on sagittal sections of cerebellar vermis, using [1251]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine1A receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine1A sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21. However, the intensity of labelling remained higher at postnatal day 8 and postnatal day 12 in X-irradiated rats than in age-paired controls. Measurements of [3H]8-OH-DPAT specific binding to membranes from whole cerebellum confirmed that the density of 5-hydroxytryptamine1A sites per mg membrane protein (Bmax) was higher in X-irradiated animals than in age-paired controls. However, on a "per cerebellum" basis, no significant difference could be detected between the total number of 5-hydroxytryptamine1A sites, which progressively increased in both control and X-irradiated animals during the first postnatal month. These results therefore show that 5-hydroxytryptamine1A receptors are not located on developing granule cells. The progressive decrease in 5-hydroxytryptamine1A receptor density during the first postnatal month did not reflect a transient expression of 5-hydroxytryptamine1A receptors in the cerebellum of newborn rats, but resulted from the progressive "dilution" of these sites in this growing structure. The higher density of 5-hydroxytryptamine1A sites in X-irradiated rats simply reflected a lower "dilution" due to the delayed growth of the cerebellum in these animals.

摘要

在出生后的第一个月内,对正常小脑以及出生后第5天经X射线照射产生颗粒细胞缺失的小脑的大鼠,研究了5-羟色胺1A受体。使用[125I]BH-8-MeO-N-PAT作为放射性配体或特异性抗受体抗体,对小脑蚓部矢状切片进行定量放射自显影研究,结果显示5-羟色胺1A受体存在于分子层/浦肯野细胞层,但不同小叶的密度各不相同。因此,在正常和经X射线照射的大鼠中,后叶的标记比前叶更重,并且在所有小脑小叶中,5-羟色胺1A位点的密度在出生后第21天逐渐降低至几乎检测不到的水平。然而,在出生后第8天和第12天,经X射线照射的大鼠的标记强度仍高于年龄匹配的对照组。对来自整个小脑的膜进行[3H]8-OH-DPAT特异性结合测量证实,经X射线照射的动物每毫克膜蛋白中5-羟色胺1A位点的密度(Bmax)高于年龄匹配的对照组。然而,以“每个小脑”为基础,在出生后的第一个月内,对照组和经X射线照射的动物中5-羟色胺1A位点的总数均逐渐增加,两者之间未检测到显著差异。因此,这些结果表明5-羟色胺1A受体并不位于发育中的颗粒细胞上。出生后第一个月内5-羟色胺1A受体密度的逐渐降低并非反映新生大鼠小脑中5-羟色胺1A受体的短暂表达,而是由于这些位点在这个不断生长的结构中逐渐“稀释”所致。经X射线照射的大鼠中5-羟色胺1A位点密度较高仅仅反映了由于这些动物小脑生长延迟导致的较低“稀释”。

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