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Tau is a microtubule (MT)-associated protein that is localized to the axon. In Alzheimer's disease, the distribution of tau undergoes a remarkable alteration, leading to the formation of tau inclusions in the somatodendritic compartment. To investigate how this mislocalization occurs, we recently developed immunohistochemical tools that can separately detect endogenous mouse and exogenous human tau with high sensitivity, which allows us to visualize not only the pathological but also the pre-aggregated tau in mouse brain tissues of both sexes. Using these antibodies, we found that in tau-transgenic mouse brains, exogenous human tau was abundant in dendrites and somata even in the presymptomatic period, whereas the axonal localization of endogenous mouse tau was unaffected. In stark contrast, exogenous tau was properly localized to the axon in human tau knock-in mice. We tracked this difference to the temporal expression patterns of tau. Endogenous mouse tau and exogenous human tau in human tau knock-in mice exhibited high expression levels during the neonatal period and strong suppression into the adulthood. However, human tau in transgenic mice was expressed continuously and at high levels in adult animals. These results indicated the uncontrolled expression of exogenous tau beyond the developmental period as a cause of mislocalization in the transgenic mice. Superresolution microscopic and biochemical analyses also indicated that the interaction between MTs and exogenous tau was impaired only in the tau-transgenic mice, but not in knock-in mice. Thus, the ectopic expression of tau may be critical for its somatodendritic mislocalization, a key step of the tauopathy. SIGNIFICANCE STATEMENT Somatodendritic localization of tau may be an early step leading to the neuronal degeneration in tauopathies. However, the mechanisms of the normal axonal distribution of tau and the mislocalization of pathological tau remain obscure. Our immunohistochemical and biochemical analyses demonstrated that the endogenous mouse tau is transiently expressed in neonatal brains, that exogenous human tau expressed corresponding to such tau expression profile can distribute into the axon, and that the constitutive expression of tau into adulthood (e.g., human tau in transgenic mice) results in abnormal somatodendritic localization. Thus, the expression profile of tau is tightly associated with the localization of tau, and the ectopic expression of tau in matured neurons may be involved in the pathogenesis of tauopathy.

書誌情報のみ, Bibliographic data Only

The Takase River, a mild slope river from a brackish water lake named Lake Ogawara, has a wide shallow area in the middle reach of the channel. Saline water intrusion to the lake is probably influenced by the existence of the shallow area. In this study, an extensive field measurement was carried out using 18 salinity meters, 68 thermometers and 3 current meters in order to investigate the flow characteristics in the shallow area and its influence upon the vertical flow structure in the low-water channel. The measurement results showed that the flow retardation in the shallow area intensifies the density stratification in the low-water channel in rising tides. This finding is consistent with the salinity record obtained at a monitoring station near the lake.

小川原湖は青森県東部の汽水湖でヤマトシジミの産地である. しかし, 湖の平常時の塩分は約1psuであり, シジミの産卵に適していると言われる値よりも低い. そこで, 本研究では小川原湖にシジミが多く生息する理由を, 現地観測と数値シミュレーションにより水理学的観点から検討した. その結果, 北東部湖口付近の浅瀬では, 比較的大規模な塩水侵入時に産卵・発生に適した塩分環境が形成されること, そのような規模の塩水侵入がシジミの産卵期に比較的高い頻度で発生することなどが示された. また, 湖北東部で発生したシジミの浮遊幼生が1週間前後の浮遊幼生期に湖水流動によって拡散し, 湖内の全域に分布する可能性が数値シミュレーションにより示唆された. 以上より, 小川原湖におけるヤマトシジミの再生産は, 主に湖北東部の浅瀬において行われているものと推定された.

Field measurements were carried out on the flow field caused by seawater intrusion in a shallow water area near the outlet of the Lake Ogawara. 64 thermometers and 6 salinity meters were placed in the area for six days. First, a correlation between the temperature increment and the salinity was investigated with an expectation that the behavior of the intruding saline water could be estimated by the temperature data because the seawater temperature was lower than the lake water temperature in the period of the measurements. The results show that the expectation was realistic for the rising tide phase but not for the sinking tide phase. A series of detailed contour maps of salinity are obtained for the rising tide phase from the temperature data analysis. The maps clearly show that the saline water spreads widely over the shallow water area although it goes up the waterway along the north shore of the lake just at the beginning of an intrusion event. The salinity data obtained at several points show that high salinity water tends to stay for over ten hours at the bottom of the shallow area after the lake water starts to outflow at the sinking tide phase.

書誌情報のみ, Bibliographic data Only