Wei Wang

With growing concerns of the safety of nanotechnology, the in vivo toxicity of nanoparticles (NPs) at environmental relevant concentrations has drawn increasing attentions. We investigated the possible molecular mechanisms of titanium nanoparticles (Ti-NPs) in the induction of toxicity at predicted environmental relevant concentrations. In nematodes, small sizes (4 nm and 10 nm) of TiO₂-NPs induced more severe toxicities than large sizes (60 nm and 90 nm) of TiO₂-NPs on animals using lethality, growth, reproduction, locomotion behavior, intestinal autofluorescence, and reactive oxygen species (ROS) production as endpoints. Locomotion behaviors could be significantly decreased by exposure to 4-nm and 10-nm TiO₂-NPs at concentration of 1 ng/L in nematodes. Among genes required for the control of oxidative stress, only the expression patterns of sod-2 and sod-3 genes encoding Mn-SODs in animals exposed to small sizes TiO₂-NPs were significantly different from those in animals exposed to large sizes of TiO₂-NPs. sod-2 and sod-3 gene expressions were closely correlated with lethality, growth, reproduction, locomotion behavior, intestinal autofluorescence, and ROS production in TiO₂-NPs-exposed animals. Ectopically expression of human and nematode Mn-SODs genes effectively prevented the induction of ROS production and the development of toxicity of TiO₂-NPs. Therefore, the altered expression patterns of Mn-SODs may explain the toxicity formation for different sizes of TiO₂-NPs at predicted environmental relevant concentrations. In addition, we demonstrated here a strategy to investigate the toxicological effects of exposure to NPs upon humans by generating transgenic strains in nematodes for specific human genes.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. For decades, the unilateral 6‑hydroxydopamine (6‑OHDA) rat model has been employed to investigate the pathogenesis and therapy of PD. However, the behavior and associated pathological features of the model long term have not previously been described dynamically. In the present study, the unilateral model was established by 6‑OHDA injection in the striatum. The PD rat model was determined 2 weeks following surgery, according to the apomorphine (APO)‑induced rotations, cylinder, rotarod and open field tests. TH‑positive neurons and fibers in the substantia nigra pars compacta (SNpc) and striatum, respectively, and glial activation in the SNpc, determined by glial fibrillary acidic protein (GFAP) expression for astrocytes and CD11b (Mac1) expression for microglia, were detected by immunohistological staining. Correlation analysis was performed to understand the association between PD‑associated behavior and pathology. The behavioral impairment progressively deteriorated during the process of experiment. In addition, the decrease in TH‑positive neurons was associated with an increase in GFAP‑ and Mac1‑positive cells in the SNpc. Linear regression analysis indicated the association between behavioral and pathological changes. The results of the present study indicate that the APO‑induced rotation, cylinder and rotarod tests are all sensitive and reliable strategies to predict the loss of TH+ neurons. These results provide a potential intervention time‑point and a comprehensive evaluation index system for assessment of PD therapeutic strategies using the hemiparkinsonian rat.