Engin Ayse Basak, Engin Atilla
Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Department of General Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey.
Prog Brain Res. 2019;245:281-303. doi: 10.1016/bs.pbr.2019.03.005. Epub 2019 Apr 2.
Although the use of nanoparticles for neuro-diagnostic and neurotherapeutic purposes provides superior benefits than the conventional approaches, it may be potentially toxic in central nervous system. In this respect, nanotechnological research focuses on nanoneurotoxicity-nanoneurosafety concepts. Despite these efforts, nanoparticles (NPs) may cause neurotoxicity, neuroinflammation, and neurodegeneration by penetrating the brain-olfactory route and blood-brain barrier (BBB). Indeed, due to their unique structures nanomaterials can easily cross biological barriers, thus avoid drug delivery problems. Despite the advancement of nanotechnology for designing therapeutic agents, toxicity of these nanomaterials is still a concern. Activation of neurons by astrocytic glutamate is a result of NPs-mediated astrocyte-neuron crosstalk. Increased extracellular glutamate levels due to enhanced synthesis and reduced reuptake may induce neuronal damage by abnormal activation of extrasynaptic N-methyl d-aspartate receptor (NMDAR) subunits. NMDAR is the key factor that mediates the disturbances in intracellular calcium homeostasis, mitochondrial dysfunction and generation of reactive oxygen species in NPs exposed neurons. While some NPs cause neuronal death by inducing NMDARs, others may be neurotoxic through the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors or protect the neurons via blocking NMDARs. However, mechanisms of dual effects of NPs, neurotoxicity or neuroprotection are not precisely known. Some NPs present neuroprotective effect either by selectively inhibiting extrasynaptic subunit of NMDARs or by attenuating oxidative stress. NPs-related proinflammatory activation of microglia contributes to the dysfunction and cytotoxicity in neurons. Therefore, investigation of the interaction of NPs with the neuronal signaling molecules and neuronal receptors is necessary for the better understanding of the neurotoxicity or neurosafety of nanomaterials.
尽管将纳米颗粒用于神经诊断和神经治疗目的比传统方法具有更大的优势，但它在中枢神经系统中可能具有潜在毒性。在这方面，纳米技术研究聚焦于纳米神经毒性 - 纳米神经安全性概念。尽管做出了这些努力，纳米颗粒（NPs）仍可能通过穿透脑 - 嗅觉途径和血脑屏障（BBB）导致神经毒性、神经炎症和神经退行性变。事实上，由于其独特的结构，纳米材料能够轻易穿过生物屏障，从而避免了药物递送问题。尽管纳米技术在设计治疗剂方面取得了进展，但这些纳米材料的毒性仍然是一个令人担忧的问题。星形胶质细胞谷氨酸对神经元的激活是NPs介导的星形胶质细胞 - 神经元相互作用的结果。由于合成增加和再摄取减少导致细胞外谷氨酸水平升高，可能通过突触外N - 甲基 - D - 天冬氨酸受体（NMDAR）亚基的异常激活诱导神经元损伤。NMDAR是介导暴露于NPs的神经元细胞内钙稳态紊乱、线粒体功能障碍和活性氧生成的关键因素。虽然一些NPs通过诱导NMDARs导致神经元死亡，但其他NPs可能通过α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）受体具有神经毒性，或者通过阻断NMDARs来保护神经元。然而，NPs双重作用（神经毒性或神经保护）的机制尚不完全清楚。一些NPs通过选择性抑制NMDARs的突触外亚基或减轻氧化应激呈现神经保护作用。NPs相关的小胶质细胞促炎激活导致神经元功能障碍和细胞毒性。因此，研究NPs与神经元信号分子和神经元受体的相互作用对于更好地理解纳米材料的神经毒性或神经安全性是必要的。
