Early detection of redox imbalance in the APPswe/PS1dE9 mouse model of Alzheimer's disease by in vivo electron paramagnetic resonance imaging.

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. Deposition of amyloid-ß (Aß) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by the generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and is known to occur early in its course. Several reports have suggested a relationship between changes in redox status and AD pathology, including progressive Aß deposition, glial cell activation, and inflammation. In the present study, we employed a newly designed three-dimensional continuous-wave digital electron paramagnetic resonance (EPR) imager with a blood-brain barrier (BBB)-permeable redox-sensitive piperidine nitroxide probe, 4-oxo-2,2,6,6-tetramethyl-piperidine-d16-1-oxyl, for early detection of changed brain redox status. Using this system, we noninvasively compared age-matched 7-month-old AD model mice with normal littermates (WT mice). The obtained brain redox images of AD and WT mice clearly showed impaired brain redox status of AD mice compared to WT, suggesting that oxidative damage had already increased in 7-month-old AD mice compared with age-matched WT mice. The pathological changes in 7-month-old mice in this study were detected earlier than in previous studies in which only AD mice older than 9 months of age could be imaged. Since EPR images suggested that oxidative damage was already increased in 7-month-old AD mice compared to age-matched WT mice, we also evaluated antioxidant levels and the activity of superoxide dismutase (SOD) in brain tissue homogenates of 7-month-old AD and WT mice. Compared to WT mice, decreased levels of glutathione and mitochondrial SOD activity were found in AD mice, which supports the EPR imaging results indicating impaired brain redox status. These results indicate that the EPR imaging method developed in this study is useful for early noninvasive detection of altered brain redox status due to oxidative disease.

Usefulness of the newly developed artificial denture plaque for practical denture care training.

OBJECTIVES: The aim of this study was to investigate whether the newly developed artificial dental plaque (A-DP) is useful as an educational tool for denture care of dental hygienist that compared it with conventional artificial dental plaque from the viewpoint of practical skills. MATERIAL AND METHODS: The 125 dental hygienist school students and 26 dental hygienists who had clinical experience were subjected a practical training of denture plaque control using the conventional denture plaque (C-DP) and the A-DP. The questionnaires based on the semantic differential method were used to survey whether the A-DP is similar to the real denture plaque (R-DP). Factor analysis by rotation of promax was carried out. RESULTS: In the results of the factor analysis, the two factors could be detected in students and three factors in dental hygienists. The total score of each denture plaque was calculated for each factor, and correlation coefficient was examined. There was significant correlation between the A-DP and the R-DP at the first factors, both students and dental hygienists. C-DP was not similar to R-DP in all factors. CONCLUSIONS: These results suggested that A-DP resembles R-DP better than C-DP. It was concluded that the A-DP was similar to the R-DP and could be a potent educational tool for practical denture care.

Alteration of masticatory function by diet change induces stress responses in Wistar rats.

The occlusion-mastication system has extradigestive functions; however, whether liquid feeding evokes stress responses remains unclear. In this study, reactions to low masticatory performance were analyzed using a diet-alteration model in Wistar rats. Seven days after the diet of the rats was changed from solid to liquid, serum epinephrine and norepinephrine concentrations were found to be elevated by 205% and 158% compared to baseline values, respectively. Superoxide production by peritoneal neutrophils was higher in rats fed with a liquid diet than in those fed with a solid diet. Serum superoxide dismutase activity (i.e. the potential to eradicate serum superoxide) was lower in rats fed with liquid than in those fed with a solid diet, indicating that the former experienced oxidative stress. Conversely, the oxidative stress was removed following reversion of the liquid diet to solid diet. These results suggest that liquid diet mastication can cause mental stress, including an oxidative stress response.

Mapping of redox status in a brain-disease mouse model by three-dimensional EPR imaging.

Electron paramagnetic resonance imaging using nitroxides is a powerful method for visualizing the redox status modulated by oxidative stress in vivo. Typically, however, data acquisition times have been too slow to obtain a sufficient number of projections for three-dimensional images, when using continuous wave-electron paramagnetic resonance imager in small rodents, using nitroxides with comparatively short T(2) and a half-life values. Because of improvements in imagers that enable rapid data-acquisition, the feasibility of three-dimensional electron paramagnetic resonance imaging with good quality in mice was tested with nitroxides. Three-dimensional images of mice were obtained at an interval of 15 sec under field scanning of 0.3 sec and with 46 projections in the case of strong electron paramagnetic resonance signals. Three-dimensional electron paramagnetic resonance images of a blood brain barrier-permeable nitroxide, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl, in the mouse head clearly showed that 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl was distributed within brain tissues, and this was confirmed by MRI observations. Based on the pharmacokinetics of nitroxides in mice, half-life mapping was demonstrated in an ischemia-reperfusion model mouse brain. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in mouse head under oxidative stress by the improved continuous wave-electron paramagnetic resonance imager noninvasively.

Effect of mastication on functional recoveries after permanent middle cerebral artery occlusion in rats.

OBJECTIVES: We evaluated whether solid feed is more effective for functional recoveries than liquid feed in rats with ischemic brain injury after permanent middle cerebral artery occlusion (MCAO). METHODS: A total of 36 male Wistar/ST rats were subjected to MCAO or sham surgery. After MCAO or sham surgery, all rats were provided liquid feed for 14 days. Then, all rats were divided into 3 groups: the solid feeding group, the liquid feeding group, and the solid feeding group of sham. Effect of mastication on functional recoveries after permanent MCAO in rats was evaluated by the limb placement test and Morris water maze (MWM) task. RESULTS: After surgery, limb placement test scores were equal in both MCAO groups. In the acquisition trials of MWM task, statistically significant differences in escape latency were observed between the liquid feeding group and sham groups at all days, and between the solid feeding group and sham groups at days 3 and 4 of the trials. In the probe trial, statistically significant differences in time spent were observed between the liquid feeding group and sham group. On day 5 of acquisition trials, the time spent in the periphery of the pool in MWM task was significantly different among the 3 groups. CONCLUSION: This study suggested that solid diet mastication could be effective for the rehabilitation of sensorimotor and learning/memory dysfunction induced by cerebral infarction.