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年龄相关性神经退行性疾病中松果体钙化的微观形态学

Micromorphology of pineal gland calcification in age-related neurodegenerative diseases.

作者信息

Bukreeva Inna, Junemann Olga, Cedola Alessia, Brun Francesco, Longo Elena, Tromba Giuliana, Wilde Fabian, Chukalina Marina V, Krivonosov Yuri S, Dyachkova Irina G, Buzmakov Alexey V, Zolotov Denis A, Palermo Francesca, Gigli Giuseppe, Otlyga Dmitry A, Saveliev Sergey V, Fratini Michela, Asadchikov Victor E

机构信息

Institute of Nanotechnology - CNR, Rome unit, Rome, Italy.

Research Institute of Human Morphology, Moscow, Russian Federation.

出版信息

Med Phys. 2023 Mar;50(3):1601-1613. doi: 10.1002/mp.16080. Epub 2022 Nov 26.

Abstract

BACKGROUND

The formation of concrements in human pineal gland (PG) is a physiological process and, according to many researchers, is associated with the involution of PG structures. The majority of scientific publications concern progressive calcification of PG, leaving out studies on the destruction of already formed calcified concrements. Our study fills the gap in knowledge about calcified zones destruction in PG in normal aging and neuropathological conditions, which has not been addressed until now.

PURPOSE

Our objective is to gain insight into human PG tissue impairment in both normal aging and neurodegenerative conditions. X-ray phase-contrast tomography (XPCT) allowed us to study PG tissue degeneration at high spatial resolution and, for the first time, to examine the damaged PG concrements in detail. Our research finding could potentially enhance the understanding of the PG involvement in the process of aging as well as in Alzheimer's disease (AD) and vascular dementia (VD).

METHODS

The research was carried out on human PG autopsy material in normal aging, VD, and AD conditions. Laboratory-based micro-computed tomography (micro-CT) was used to collect and evaluate samples of native, uncut, and unstained PG with different degrees of pineal calcification. The detailed high-resolution 3D images of the selected PGs were produced using synchrotron-based XPCT. Histology and immunohistochemistry of soft PG tissue confirmed XPCT results.

RESULTS

We performed via micro-CT the evaluation of the morphometric parameters of PG such as total sample volume, calcified concrements volume, and percentage of concrements in the total volume of the sample. XPCT imaging revealed high-resolution details of age-related PG alteration. In particular, we noted signs of moderate degradation of concrements in some PGs from elderly donors. In addition, our analysis revealed noticeable degenerative change in both concrements and soft tissue of PGs with neuropathology. In particular, we observed a hollow core and separated layers as well as deep ragged cracks in PG concrements of AD and VD samples. In parenchyma of some samples, we detected wide pinealocyte-free fluid-filled areas adjacent to the calcified zones.

CONCLUSION

The present work provides the basis for future scientific research focused on the dynamic nature of PG calcium deposits and PG soft tissue in normal aging and neurodegenerative diseases.

摘要

背景

人类松果体(PG)中 concretions 的形成是一个生理过程,许多研究人员认为,这与 PG 结构的退化有关。大多数科学出版物关注的是 PG 的渐进性钙化,而忽略了对已形成的钙化 concretions 破坏情况的研究。我们的研究填补了在正常衰老和神经病理条件下 PG 钙化区域破坏方面的知识空白,这一空白至今尚未得到解决。

目的

我们的目标是深入了解正常衰老和神经退行性疾病中人类 PG 组织的损伤情况。X 射线相衬断层扫描(XPCT)使我们能够在高空间分辨率下研究 PG 组织的退化,并首次详细检查受损的 PG concretions。我们的研究结果可能会增进对 PG 在衰老过程以及阿尔茨海默病(AD)和血管性痴呆(VD)中所起作用的理解。

方法

该研究对正常衰老、VD 和 AD 条件下的人类 PG 尸检材料进行。基于实验室 的微型计算机断层扫描(micro-CT)用于收集和评估不同松果体钙化程度的天然、未切割和未染色的 PG 样本。使用基于同步加速器的 XPCT 生成所选 PG 的详细高分辨率 3D 图像。软 PG 组织的组织学和免疫组织化学证实了 XPCT 结果。

结果

我们通过 micro-CT 评估了 PG 的形态学参数,如总样本体积、钙化 concretions 体积以及 concretions 在样本总体积中的百分比。XPCT 成像揭示了与年龄相关的 PG 改变的高分辨率细节。特别是,我们注意到老年捐赠者的一些 PG 中 concretions 有中度降解的迹象。此外,我们的分析显示,患有神经病理学的 PG 的 concretions 和软组织都有明显的退行性变化。特别是,我们在 AD 和 VD 样本的 PG concretions 中观察到空心核心和分离层以及深深的参差不齐的裂缝。在一些样本的实质中,我们在钙化区域附近检测到宽阔的无松果体细胞的充满液体的区域。

结论

本研究为未来聚焦于正常衰老和神经退行性疾病中 PG 钙沉积物及 PG 软组织动态性质的科学研究提供了基础。

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