College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin, 300071, China.
Neurotox Res. 2019 Nov;36(4):736-745. doi: 10.1007/s12640-019-00075-1. Epub 2019 Jun 20.
Fullerene is a family of carbon materials widely applied in modern medicine and ecosystem de-contamination. Its wide application makes human bodies more and more constantly exposed to fullerene particles. Since fullerene particles are able to cross the blood-brain barrier (BBB) (Yamago et al. 1995), if and how fullerene would affect brain functions need to be investigated for human health consideration. For this purpose, we administered fullerene on subcortical ischemic vascular dementia (SIVD) model mice and sham mice, two types of mice with distinct penetration properties of BBB and hence possibly distinct vulnerabilities to fullerene. We studied the spatial learning and memory abilities of mice with Morris water maze (MWM) and the neuroplasticity properties of the hippocampus. Results showed that fullerene administration suppressed outcomes of MWM in sham mice, along with suppressed long-term potentiation (LTP) and dendritic spine densities. Oppositely, recoveries of MWM outcomes and neuroplasticity properties were observed in fullerene-treated SIVD mice. To further clarify the mechanism of the impact of fullerene on neuroplasticity, we measured the levels of postsynaptic density protein 95 (PSD-95), synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) by western blot assay. Results suggest that the distinct impacts of fullerene on behavior test and neuroplasticity may be conducted through postsynaptic regulations that were mediated by BDNF.
富勒烯是一类广泛应用于现代医学和生态系统净化的碳材料。由于其广泛的应用,人类的身体越来越多地不断暴露在富勒烯颗粒中。由于富勒烯颗粒能够穿过血脑屏障(BBB)(Yamago 等人,1995 年),因此需要研究富勒烯是否以及如何影响大脑功能,以考虑人类健康。为此,我们在皮质下缺血性血管性痴呆(SIVD)模型小鼠和假手术小鼠上给予富勒烯,这两种小鼠的 BBB 穿透特性不同,因此可能对富勒烯的敏感性不同。我们使用 Morris 水迷宫(MWM)研究了小鼠的空间学习和记忆能力,以及海马的神经可塑性特性。结果表明,富勒烯处理抑制了假手术小鼠的 MWM 结果,同时抑制了长时程增强(LTP)和树突棘密度。相反,在富勒烯处理的 SIVD 小鼠中观察到 MWM 结果和神经可塑性特性的恢复。为了进一步阐明富勒烯对神经可塑性影响的机制,我们通过 Western blot 测定测量了突触后密度蛋白 95(PSD-95)、突触小体相关蛋白(SYP)、脑源性神经营养因子(BDNF)和原肌球蛋白受体激酶 B(TrkB)的水平。结果表明,富勒烯对行为测试和神经可塑性的不同影响可能通过 BDNF 介导的突触后调节来实现。