Singhrao Sim K, Chukkapalli Sasanka, Poole Sophie, Velsko Irina, Crean St John, Kesavalu Lakshmyya
Dementia and Neurodegeneration Research Group, College of Clinical and Biomedical Sciences, University of Central Lancashire , Preston , UK.
Department of Periodontology, University of Florida , Gainesville , FL , USA.
J Oral Microbiol. 2017 Jan 17;9(1):1270602. doi: 10.1080/20002297.2016.1270602. eCollection 2017.
This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE) B6 background mice brains following chronic gingival infection with for 24 weeks. Intracerebral localization of was detected by fluorescence hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of cells ( = 0.001). PAS and silver impregnation demonstrated the presence of larger inclusions restricted to the CA1, CA2, and dentate gyrus sectors of the hippocampus. A specific monoclonal antibody to bacterial peptidoglycan detected clusters of granules with variable sizes in mice brains infected with ( = 0.004), and also highlighted areas of diffuse punctate staining equating to physical tissue damage. Mouse immunoglobulin G was observed in the capillaries of the cerebral parenchyma of all -infected brains ( = 0.001), and on pyramidal neurons in some severely affected mice, compared with the sham-infected mice. Gingipains was also observed in microvessels of the hippocampus in the infected mice. This study supports the possibility of early appearance of age-related granules in ApoE mice following inflammation-mediated tissue injury, accompanied by loss of cerebral blood-brain barrier integrity.
本研究探讨了载脂蛋白E基因敲除（ApoE）B6背景小鼠在慢性牙龈感染24周后脑内与年龄相关颗粒的起源。通过荧光原位杂交（FISH）检测其在脑内的定位，并通过免疫组织化学检测其蛋白酶。通过过碘酸希夫（PAS）染色、银浸染和免疫染色观察与年龄相关的颗粒。FISH显示细胞在脑内播散（P = 0.001）。PAS染色和银浸染显示海马体的CA1、CA2和齿状回区域存在较大的包涵体。一种针对细菌肽聚糖的特异性单克隆抗体在感染的小鼠脑中检测到大小不一的颗粒簇（P = 0.004），并且还突出了等同于物理组织损伤的弥漫性点状染色区域。与假感染小鼠相比，在所有感染的小鼠脑实质毛细血管中均观察到小鼠免疫球蛋白G（P = 0.001），在一些严重受影响的小鼠的锥体神经元上也观察到。在感染小鼠的海马体微血管中也观察到牙龈蛋白酶。本研究支持在炎症介导的组织损伤后，ApoE小鼠中与年龄相关颗粒早期出现的可能性，同时伴有脑血脑屏障完整性的丧失。
