Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer's Disease Patient.

Journal of Neurodegenerative Diseases Pub Date : 2013-01-01 Epub Date: 2013-05-16 DOI:10.1155/2013/879710
Amrutha Chilumuri, Maria Ashioti, Amanda N Nercessian, Nathaniel G N Milton
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引用次数: 12

Abstract

The pons region of the Alzheimer's disease (AD) brain is one of the last to show amyloid-β (Aβ) deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH) and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits. Results showed Aβ deposits also stained with KP, CRH, and catalase antibodies. At high magnification the staining of deposits was either KP or catalase positive, and there was only a limited area of the deposits with KP-catalase colocalization. The CRH does not bind Aβ, whilst both KP and catalase can bind Aβ, suggesting that colocalization in Aβ deposits is not restricted to compounds that directly bind Aβ. The neuroprotective actions of KP, CRH, and catalase were confirmed in vitro, and fibrillar Aβ preparations were shown to stimulate the release of KP in vitro. In conclusion, neuroprotective KP, CRH, and catalase all colocalize with Aβ plaque-like deposits in the pons region from a male AD subject.

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与阿尔茨海默病患者脑桥淀粉样蛋白-β沉积相关的Kisspeptin免疫定位
阿尔茨海默病(AD)大脑的脑桥区域是最后显示淀粉样蛋白-β (Aβ)沉积的区域之一,并被认为含有神经保护化合物。Kisspeptin (KP)是一种激活下丘脑-垂体-性腺轴的激素,已被认为对a β毒性具有神经保护作用。KP的定位,加上内源性神经保护化合物促肾上腺皮质激素释放激素(CRH)和过氧化氢酶,在男性AD受试者的脑桥区域的组织切片中被确定与a β沉积有关。结果显示,Aβ沉积物也被KP、CRH和过氧化氢酶抗体染色。在高倍镜下,沉积物的染色为KP或过氧化氢酶阳性,只有有限区域的沉积物与KP-过氧化氢酶共定位。CRH不结合Aβ,而KP和过氧化氢酶都可以结合Aβ,这表明在Aβ沉积物中的共定位并不局限于直接结合Aβ的化合物。体外实验证实了KP、CRH和过氧化氢酶的神经保护作用,纤维β制剂可刺激KP的体外释放。综上所述,男性AD患者的神经保护KP、CRH和过氧化氢酶均与脑桥区a β斑块样沉积物共定位。
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