Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic" - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
NanoLab, Biomedical Engineering, Faculty of Mechanical Engineering, University of Belgrade, Belgrade, Serbia.
CNS Neurosci Ther. 2024 Mar;30(3):e14188. doi: 10.1111/cns.14188. Epub 2023 Mar 27.
In the present study, we assessed the effects of the hyper-harmonized-hydroxylated fullerene-water complex (3HFWC) on Alzheimer's disease (AD) neuropathological hallmarks in 5XFAD mice, an AD animal model.
The 3-week-old 5XFAD mice were exposed to 3HFWC water solution ad libitum for 3 months in the presymptomatic phase of pathology. The functional effects of the treatment were confirmed through near-infrared spectroscopy (NIRS) analysis through machine learning (ML) using artificial neural networks (ANNs) to classify the control and 3HFWC-treated brain tissue samples. The effects of 3HFWC treatment on amyloid-β (Aβ) accumulation, plaque formation, gliosis, and synaptic plasticity in cortical and hippocampal tissue were assessed.
The 3HFWC treatment significantly decreased the amyloid-β plaque load in specific parts of the cerebral cortex. At the same time, 3HFWC treatment did not induce the activation of glia (astrocytes and microglia) nor did it negatively affect synaptic protein markers (GAP-43, synaptophysin, and PSD-95).
The obtained results point to the potential of 3HFWC, when applied in the presymptomatic phase of AD, to interfere with amyloid plaque formation without inducing AD-related pathological processes such as neuroinflammation, gliosis, and synaptic vulnerability.
在本研究中，我们评估了超调和羟基化富勒烯水合物复合物（3HFWC）对 5XFAD 小鼠（一种 AD 动物模型）阿尔茨海默病（AD）神经病理学特征的影响。
3 周龄的 5XFAD 小鼠在病理学的前驱期自由暴露于 3HFWC 水溶液中 3 个月。通过近红外光谱（NIRS）分析，使用人工神经网络（ANN）的机器学习（ML）对治疗的功能效果进行了确认，通过 ANN 对对照和 3HFWC 处理的脑组织样本进行分类。评估了 3HFWC 处理对皮质和海马组织中淀粉样β（Aβ）积累、斑块形成、神经胶质增生和突触可塑性的影响。
3HFWC 处理显著降低了大脑皮质特定部位的淀粉样β斑块负荷。同时，3HFWC 处理不会诱导神经胶质（星形胶质细胞和小胶质细胞）的激活，也不会对突触蛋白标志物（GAP-43、突触小体和 PSD-95）产生负面影响。
研究结果表明，3HFWC 在 AD 的前驱期应用时具有潜力，可在不诱导 AD 相关病理过程（如神经炎症、神经胶质增生和突触脆弱性）的情况下干扰淀粉样斑块的形成。
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