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阿尔茨海默病中组胺能系统的改变:一项尸检研究。

Alterations in the histaminergic system in Alzheimer's disease: a postmortem study.

机构信息

Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Neurobiol Aging. 2012 Nov;33(11):2585-98. doi: 10.1016/j.neurobiolaging.2011.12.026. Epub 2012 Jan 26.

DOI:10.1016/j.neurobiolaging.2011.12.026
PMID:22284987
Abstract

Histamine is produced by the hypothalamic tuberomamillary nucleus (TMN). We studied its involvement in Alzheimer's disease (AD) by in situ hybridization of histidine decarboxylase (HDC), the key enzyme of histamine production, in 9 AD patients and 9 controls. Additionally, messenger (m) RNA levels of the 4 histamine receptors (H(1-4)R) and of the enzyme involved in histamine metabolism, histamine methyltransferase (HMT), were determined by quantitative polymerase chain reaction (qPCR) in the prefrontal cortex (PFC) in the course of AD (n = 49). Moreover, alterations in glia markers were studied. HDC-mRNA levels in the TMN were unchanged in AD, despite of the reduced number of Nissl-stained neurons (p = 0.001). However, a decrease in HDC-mRNA was observed in its medial part (mTMN; p = 0.047). In the course of AD only females had increased prefrontal cortex expression of histamine receptor-3 (H(3)R) (p = 0.007) and histamine methyltransferase-mRNA (p = 0.011) and of the glia markers, glial fibrillary acidic protein-mRNA, vimentin-mRNA and proteolipid protein-mRNA. These findings indicate the presence of regional changes in the TMN that are at least partly gender-dependent.

摘要

组胺是由下丘脑结节乳头核(TMN)产生的。我们通过原位杂交研究了组氨酸脱羧酶(HDC)——组胺产生的关键酶,来研究其在阿尔茨海默病(AD)中的作用,共纳入 9 名 AD 患者和 9 名对照者。此外,我们通过定量聚合酶链反应(qPCR)在 AD 患者的额前皮质(PFC)中测定了 4 种组胺受体(H(1-4)R)和参与组胺代谢的酶——组胺甲基转移酶(HMT)的信使(m)RNA 水平(n = 49)。此外,我们还研究了神经胶质细胞标志物的改变。AD 患者 TMN 中的 HDC-mRNA 水平不变,尽管尼氏染色神经元数量减少(p = 0.001)。然而,在 TMN 的中部(mTMN)观察到 HDC-mRNA 的减少(p = 0.047)。在 AD 中,只有女性的额前皮质组胺受体 3(H(3)R)(p = 0.007)和组胺甲基转移酶-mRNA(p = 0.011)以及神经胶质细胞标志物胶质纤维酸性蛋白-mRNA、波形蛋白-mRNA 和蛋白脂质蛋白-mRNA 的表达增加。这些发现表明 TMN 存在区域性变化,至少部分是性别依赖性的。

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