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神经退行性蛋白病嗅球中不同的小胶质细胞增生模式。

Distinct Pattern of Microgliosis in the Olfactory Bulb of Neurodegenerative Proteinopathies.

作者信息

Kohl Zacharias, Schlachetzki Johannes C M, Feldewerth Judith, Hornauer Philipp, Münch Martina, Adame Anthony, Riemenschneider Markus J, Winkler Jürgen, Masliah Eliezer

机构信息

Department of Molecular Neurology, Friedrich-Alexander-University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany.

Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA, USA.

出版信息

Neural Plast. 2017;2017:3851262. doi: 10.1155/2017/3851262. Epub 2017 Mar 19.

Abstract

The olfactory bulb (OB) shows early neuropathological hallmarks in numerous neurodegenerative diseases, for example, in Alzheimer's disease (AD) and Parkinson's disease (PD). The glomerular and granular cell layer of the OB is characterized by preserved cellular plasticity in the adult brain. In turn, alterations of this cellular plasticity are related to neuroinflammation such as microglia activation, implicated in the pathogenesis of AD and PD, as well as frontotemporal lobe degeneration (FTLD). To determine microglia proliferation and activation we analyzed ionized calcium binding adaptor molecule 1 (Iba1) expressing microglia in the glomerular and granular cell layer, and the olfactory tract of the OB from patients with AD, PD dementia/dementia with Lewy bodies (PDD/DLB), and FTLD compared to age-matched controls. The number of Iba1 and CD68 positive microglia associated with enlarged amoeboid microglia was increased particularly in AD, to a lesser extent in FTLD and PDD/DLB as well, while the proportion of proliferating microglia was not altered. In addition, cells expressing the immature neuronal marker polysialylated neural cell adhesion molecule (PSA-NCAM) were increased in the glomerular layer of PDD/DLB and FTLD cases only. These findings provide novel and detailed insights into differential levels of microglia activation in the OB of neurodegenerative diseases.

摘要

嗅球(OB)在众多神经退行性疾病中呈现早期神经病理学特征,例如在阿尔茨海默病(AD)和帕金森病(PD)中。OB的肾小球层和颗粒细胞层的特征是在成人大脑中保留了细胞可塑性。反过来,这种细胞可塑性的改变与神经炎症有关,如小胶质细胞活化,这与AD、PD以及额颞叶变性(FTLD)的发病机制有关。为了确定小胶质细胞的增殖和活化情况,我们分析了AD、帕金森病痴呆/路易体痴呆(PDD/DLB)和FTLD患者的OB的肾小球层和颗粒细胞层以及嗅束中表达离子钙结合衔接分子1(Iba1)的小胶质细胞,并与年龄匹配的对照组进行比较。与肿大的阿米巴样小胶质细胞相关的Iba1和CD68阳性小胶质细胞数量尤其在AD中增加,在FTLD和PDD/DLB中也有一定程度的增加,而增殖性小胶质细胞的比例没有改变。此外,仅在PDD/DLB和FTLD病例的肾小球层中,表达未成熟神经元标志物多唾液酸神经细胞粘附分子(PSA-NCAM)的细胞增加。这些发现为神经退行性疾病OB中小胶质细胞活化的不同水平提供了新颖而详细的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82d5/5376461/04455e65df87/NP2017-3851262.001.jpg

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