title: Mechanisms of TiO2 nanoparticle-induced neuronal apoptosis in rat primary cultured hippocampal neurons.
abstract: Exposure to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to decrease learning and memory of animals. However, whether the impacts of these NPs on the recognition function are involved in hippocamal neuron damages is poorly understood. In this study, primary cultured hippocampal neurons from one-day-old fetal Sprague-Dawley rats were exposed to 5, 15, or 30 µg/mL TiO2 NPs for 24 h, we investigated cell viability, ultrastructure, and mitochondrial membrane potential (MMP), calcium homeostasis, oxidative stress, antioxidant capacity, apoptotic signaling pathway associated with the primary cultured hippocamal neuron apoptosis. Our findings showed that TiO2 NP treatment resulted in reduction of cell viability, promoted lactate dehydrogenase release, apoptosis, and increased neuron apoptotic rate in a dose-dependent manner. Furthermore, TiO2 NPs led to [Ca(2+)]i elevation, and MMP reduction, up-regulated protein expression of cytochrome c, Bax, caspase-3, glucose-regulated protein 78, C/EBP homologous protein and caspase-12, and down-regulated bcl-2 expression in the primary cultured hippocampal neurons. These findings suggested that hippocampal neuron apoptosis caused by TiO2 NPs may be associated with mitochondria-mediated signal pathway and endoplasmic reticulum-mediated signal pathway.
authors.affiliation: Medical College of Soochow University, Suzhou, 215123, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiao
authors.initials: X
authors.lastname: Ze
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Bingqing
authors.initials: B
authors.lastname: Xu
authors.forename: Yunting
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Long
authors.forename: Anan
authors.initials: A
authors.lastname: Lin
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles / Q000009:adverse effects* / Q000737:chemistry; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014025:Titanium / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; C009495:titanium dioxide; D014025:Titanium
keywords: calcium overload; endoplasmic reticulum-mediated signal pathway; mitochondria-mediated signal pathway; primary cultured hippocampal neurons; titanium dioxide nanoparticles