Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain

Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain
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DOI:
10.1016/j.jchemneu.2004.08.006
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发表时间:
2005-01-01
影响因子:
2.8
通讯作者:
McGrath, JJ
McGrath, JJ
中科院分区:
医学4区
文献类型:
--
作者:
Eyles, DW;Smith, S;McGrath, JJ

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尽管越来越多的证据表明维生素D参与哺乳动物的大脑功能。关于它在人脑中的作用,一直缺乏直接的证据。本文首次报道了1,25-二羟维生素D-3受体(VDR)和1 α-羟化酶(lalpha-OHase)在人脑中的分布。受体和酶被发现在神经元和神经胶质细胞中的区域和层的特定模式。VDR局限于细胞核,而1 α-OHase分布于整个细胞质。VDR在人脑中的分布与啮齿类动物中报道的分布惊人地相似。许多区域含有等量的VDR和1alpha-OHase,然而Meynert基底核(NBM)内的大细胞和小脑中的浦肯野细胞在缺乏VDR的情况下表达1alpha-OHase。最强的受体和酶的免疫组织化学染色是在下丘脑和黑质内的大(推测多巴胺能)神经元。观察到的VDR分布与维生素D以与已知神经类固醇类似的方式起作用的提议一致。1 α-羟化酶和维生素D受体的广泛分布表明,维生素D在人脑中可能具有自分泌/旁分泌特性。(C)2004 Elsevier B.V.保留所有权利。
Despite a growing body of evidence that Vitamin D is involved in mammalian brain functioning. there has been a lack of direct evidence about its role in the human brain. This paper reports, for the first time, the distribution of the 1,25-dihydroxyvitamin D-3 receptor (VDR), and 1alpha-hydroxylase (lalpha-OHase), the enzyme responsible for the formation of the active vitamin in the human brain. The receptor and the enzyme were found in both neurons and glial cells in a regional and layer-specific pattern. The VDR was restricted to the nucleus whilst 1alpha-OHase was distributed throughout the cytoplasm. The distribution of the VDR in human brain was strikingly similar to that reported in rodents. Many regions contained equivalent amounts of both the VDR and 1alpha-OHase, however the macrocellular cells within the nucleus basalis of Meynert (NBM) and the Purkinje cells in the cerebellum expressed 1alpha-OHase in the absence of VDR. The strongest immunohistochemical staining for both the receptor and enzyme was in the hypothalamus and in the large (presumably dopaminergic) neurons within the substania nigra. The observed distribution of the VDR is consistent with the proposal that Vitamin D operates in a similar fashion to the known neurosteroids. The widespread distribution of 1alpha-OHase and the VDR suggests that Vitamin D may have autocrine/paracrine properties in the human brain. (C) 2004 Elsevier B.V. All rights reserved.