sakai kazuyoshi

光学顕微鏡レベルで鍍銀陽性小体(核小体様封入体)を観察するためにグルタールアルデヒド含有固定が必須であるかどうか検討した。正常ddY雄マウスを使用し、10%ホルマリン灌流固定群、2.5%グルタールアルデヒド+5%ホルマリン混合液固定群、グルタールアルデヒド0.1%、0.5%、1.0%、2.5%灌流固定群を設定した。2.5%グルタールアルデヒドと5%ホルマリン混合液固定液で1日固定した標本では鍍銀陽性小体の存在が確認できた。最初に10%ホルマリンで固定された脳組織でも、その後にグルタールアルデヒド含有固定液で再固定すれば、鍍銀陽性小体の検索が可能であることが確認された。パラフィン切片での鍍銀陽性小体である核小体様封入体の染色にはグルタール含有固定が必須であることが証明され、最適な固定液は2.5%グルタールアルデヒドと5%ホルマリンの混合液であった。

<b><i>Introduction:</i></b> Patients with dementia show reduced adaptive, behavioral, and physiological responses to environmental threats. Physical exercise is expected to delay brain aging, maintain cognitive function and, consequently, help dementia patients face threats and protect themselves skillfully. <b><i>Methods:</i></b> To confirm this, we aimed to investigate the effects of the shaking exercise on the avoidance function in the senescence-accelerated mouse-prone strain-10 (SAMP-10) model at the behavioral and tissue levels. SAMP-10 mice were randomized into 2 groups: a control group and a shaking group. The avoidance response (latency) of the mice was evaluated using a passive avoidance task. The degree of amygdala and hippocampal aging was evaluated based on the brain morphology. Subsequently, the association between avoidance response and the degree of amygdala-hippocampal aging was evaluated. <b><i>Results:</i></b> Regarding the passive avoidance task, the shaking group showed a longer latency period than the control group (<i>p</i> < 0.05), even and low intensity staining of ubiquitinated protein, and had a higher number of and larger neurons than those of the control group. The difference between the groups was more significant in the BA region of the amygdala and the CA1 region of the hippocampus (staining degree: <i>p</i> < 0.05, neuron size: <i>p</i> < 0.01, neuron counts: <i>p</i> < 0.01) than in other regions. <b><i>Conclusions:</i></b> The shaking exercise prevents nonfunctional protein (NFP) accumulation, neuron atrophy, and neuron loss; delays the aging of the amygdala and hippocampus; and maintains the function of the amygdala-hippocampal circuit. It thus enhances emotional processing and cognition functions, the memory of threats, the skillful confrontation of threats, and proper self-protection from danger.

INTRODUCTION: The disabling effects of dementia, an incurable disease with little effect on mortality, affect society far more than many other conditions. OBJECTIVE: The aim of this study was to stop or delay the onset of dementia using low-cost methods such as physical exercise. METHODS: Senescence-accelerated model-prone (SAMP) 10 mice were made to perform a user-friendly shaking exercise for 25 weeks. The motor function and hippocampal functions (learning, spatial cognition) of the mice were evaluated using behavioral experiments. The degree of hippocampal aging was evaluated based on brain morphology. The association between behavioral performance of the mice and the degree of hippocampal aging was then evaluated. RESULTS: The behavioral test results showed that the shaking group had higher motor coordination (p < 0.01) and motor learning (p < 0.05). Significantly higher performances in the learning ability were observed in the shaking group at a middle-period experiment (p < 0.05); the spatial cognitive functions also improved (p < 0.05). The shaking group showed delayed ageing of cells in the dentate gyrus (DG; area: p < 0.01) and cornu Ammonis (CA; area: p < 0.01) regions of the hippocampus. CONCLUSIONS: The shaking exercise enhances the activity of mice and reduces age-associated decreases in learning and spatial cognitive functions. Regarding hippocampal morphology, shaking exercise can prevent non-functional protein accumulation, cell atrophy, and cell loss. Specifically, shaking exercise protects cell growth and regeneration in the DG area and enhances the learning function of the hippocampus. Furthermore, shaking exercise maintained the spatial cognitive function of cells in the CA3 and CA1 regions, and prevented the chronic loss of CA2 transmission that decreased the spatial memory decline in mice.

In Japan, 13 million people have osteoporosis, including approximately 9 hundred thousand people who are bedridden owing to bone fractures from falls. Preventing osteoporosis is considered to be an important and effective way of preventing fall-related fractures. Thus, we developed a novel method of locomotor stimulation and analyzed its effectiveness in mice. Specifically, we created a double-loading device that combines vibration and shaking stimulation. The device was used to continuously stimulate ovariectomy-induced decreased bone density mouse models 30 minutes daily for 10 weeks. We then collected femur samples, created undecalcified tissue slices, calculated parameters using bone histomorphomtry, and conducted comparative testing. BS/TV (bone surface/tissue volume), N.Oc/ES (osteoclast number/eroded surface), Oc.S/ES (osteoclast osteoid surface/eroded surface), Omt (osteoid maturation time), Tb.N (trabecular number), Mlt (mineralization lag time) < (p < 0.01), N.Ob (osteoblast number), N.Ob/TV (osteoblast number/tissue volume), sLS (single labeled suface), N.Mu.Oc/ES (multinucle osteoclast number/eroded surface), and N.Mo.Oc/ES (mononucle osteoclast number/eroded surface) (p < 0.05) were significantly higher in the stimulation group than in the non-stimulation group. In addition, BS/BV (bone surface/bone volume), Tb.Sp (trabecular separation), MAR (mineral apposition rate), Aj.Ar (adjusted apposition rate) (p < 0.01), ES (eroded surface ), ES/BS (eroded surface/bone surface), and BRs.R (bone resorption rate) (p < 0.05) were significantly lower in the stimulation group than in the non-stimulation group. These results suggest that stimulation activated osteoblasts and osteoclasts, thereby leading to highly active bone remodeling. We anticipate that bone mineralization will subsequently occur, suggesting that this stimulation technique is effective in preventing osteoporosis by alleviating sudden bone density loss.

The accumulation of amyloid-β protein (Aβ) and tau in the brain is a major pathological change related to Alzheimer's disease. We have continued to develop Extracorporeal Blood Aβ Removal Systems (E-BARS) as a method for enhancing Aβ clearance from the brain. Our previous report revealed that dialyzers effectively remove blood Aβ and evoke large Aβ influxes into the blood, resulting in a decrease in brain Aβ accumulation after initiating hemodialysis, and that patients who underwent hemodialysis had lower brain Aβ accumulation than those who did not. Here, plasma total tau concentrations from 30 patients undergoing hemodialysis were measured using an ultrasensitive immunoassay and compared to those from 11 age-matched controls. Plasma total tau concentrations were higher in patients with renal failure regardless of whether they underwent hemodialysis, suggesting the involvement of the kidneys in tau degradation and excretion. Hemodialyzers effectively removed blood Aβ but not extracorporeal blood tau. The influx of tau into the blood was observed at around the 1 h period during hemodialysis sessions. However, the influx amount of tau was far smaller than that of Aβ. Furthermore, histopathological analysis revealed similar, not significantly less, cerebral cortex phosphorylated tau accumulation between the 17 patients who underwent hemodialysis and the 16 age-matched subjects who did not, although both groups showed sparse accumulation. These findings suggest that hemodialysis may induce both tau and Aβ migration into the blood. However, as a therapeutic strategy for Alzheimer's disease, it may only be effective for removing Aβ from the brain.