Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for Parkinson’s, Alzheimer’s, and psychiatric diseases

We overview the 16-kDa proteolipid mediatophore, the transmembrane c-subunit of the V0 sector of the vacuolar proton ATPase (ATP6V0C) that was shown to mediate the secretion of acetylcholine. Acetylcholine, serotonin, and dopamine (DA) are released from cell soma and/or dendrites if ATP6V0C is expressed in cultured cells. Adeno-associated viral vector-mediated gene transfer of ATP6V0C into the caudate putamen enhanced the depolarization-induced overflow of endogenous DA in Parkinson-model mice. Motor impairment was ameliorated in hemiparkinsonian model mice when ATP6V0C was expressed with DA-synthesizing enzymes. The review discusses application in the future as a potential tool for gene therapy, cell transplantation therapy, and inducible pluripotent stem cell therapy in neurological diseases, from the view point of recent findings regarding vacuolar ATPase. © 2016, The Physiological Society of Japan and Springer Japan

Dopamine release via the vacuolar ATPase V0 sector c-subunit, confirmed in N18 neuroblastoma cells, results in behavioral recovery in hemiparkinsonian mice

A 16-kDa proteolipid, mediatophore, in Torpedo electric organs mediates Ca 2+-dependent acetylcholine release. Mediatophore is identical to the pore-forming stalk c-subunit of the V0 sector of vacuolar proton ATPase (ATP6V0C). The function of ATP6V0C in the mammalian central nervous system is not clear. Here, we report transfection of adeno-associated viral vectors harboring rat ATP6V0C into the mouse substantia nigra, in which high potassium stimulation increased overflow of endogenous dopamine (DA) measured in the striatum by in vivo microdialysis. Next, in the striatum of 6-hydroxydopamine- lesioned mice, a model of Parkinson\u27s disease (PD), human tyrosine hydroxylase, aromatic l-amino-acid decarboxylase and guanosine triphosphate cyclohydrolase 1, together with or without ATP6V0C, were expressed in the caudoputamen for rescue. Motor performance on the accelerating rotarod test and amphetamine-induced ipsilateral rotation were improved in the rescued mice coexpressing ATP6V0C. [ 3H]DA, taken up into cultured N18 neuronal tumor cells transformed to express ATP6V0C, was released by potassium stimulation. These results indicated that ATP6V0C mediates DA release from nerve terminals in the striatum of DA neurons of normal mice and from gene-transferred striatal cells of parkinsonian mice. The results suggested that ATP6V0C may be useful as a rescue molecule in addition to DA-synthetic enzymes in the gene therapy of PD. © 2011 Elsevier Ltd. All rights reserved

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本研究の目的は, 弓道上段者の弓射動作の速度を具体的に明らかにすることであった。被験者は六段3名であり, 実射時の動作をハイスピードビデオカメラで撮影し分析した。結果は以下の通りである。1)打起し動作の平均速度(垂直方向)は0.11±0.01m/s, ピーク速度は0.23±0.03m/sであった。2)打起しから大三の位置までの引分け動作の平均速度(水平方向)は, 0.13±0.06m/s(左手)および0.04±0.02m/s(右手), ピーク速度は0.19±0.06m/s(左手)および0.09±0.02m/s(右手)であった。3)大三から会までの平均速度(水平方向)は, 0.02±0.01m/s(左手)および-0.07±0.02m/s(右手), ピーク速度は0.04±0.02m/s(左手)および-0.17±0.03m/s(右手)であった。4)各動作時の速度変化(水平方向)は, 等速状態はほとんどなく, 動作開始初期にピークをむかえ, 以後終点にむかって徐々に減速していた。The purpose of this study was to investigate the drawing velocity in shooting motion of skilled Japanese archers. The drawing motions of three "sixth grade" archers were filmed using a high speed video camera system. The video was analyzed by a computer for the velocity of the left(L) and right(R) hands during three different phases of motion ;"Uchiokoshi", from "Uchiokoshi" to "Daisan", and from "Daisan" to "Kai." The vertical average velocity(AV) and the peak velocity(PV) during "Uchiokoshi" were 0.11±0.01 and 0.23±0.03 m/s, respectively. From "Uchiokoshi" to "Daisan" motion, the horizontal AVs were 0.13±0.06(L) and 0.04±0.02 m/s(R), and the horizontal PVs were 0.19±0.06(L) and 0.09±0.02 m/s(R). From "Daisan" to "Kai" motion, the horizontal AVs were 0.02±0.01(L) and -0.07±0.02 m/s(R), and the horizontal PVs were 0.04±0.02(L) and -0.17±0.03 m/s(R). The velocity of motion was not constant in the three phases. The PV was observed right after the beginning of each motion, then the velocity gradually decreased toward the end of the motion. It seemed that this fast-slow movement was important for skilled drawing performance

絶食時の持久力トレーニングが骨格筋重量及びその他臓器組織重量に及ぼす影響

This experiment considered the influence on the weight of body organs, when endurancetraining was performed by a fasting state without ingestion of a nutrient. Female ICR mice (27.2g ~ 36.7g weight)were used. These mice were classified into four groups shown below, with five animals in each group. (1) Food intake and training group, (2) Food intake and nontraining group (3) non-food intake and training group (4) non-food intake and non- training group. The experiment was conducted for four days. The mice were kept in individual cages at a room temperature of 24℃. Drinking water was given freely. Four days later, mice weresacrificed by blood removal under anesthesia, and then each of the organs and tissues were collected from each mouse. Each weight was measured by electromagnetism type measure. Endurance exercise was performed using a mouse device rotating momentum. Measurement of momentum was made of a fixed time every day and the mileage was calculated. As a result ofobserving the influence which it has on weight in each internal-organ of body, the influence by a meal reflected the weight of internal organs strongly. Both a meal and movement influenced the weight of the soleus muscle. In the case of plantaris, it was the same as that of a soleus muscle. However, as for plantaris, as compared with the soleus muscle, the influence of a mealwas more strongly observed from comparison of B group and D group. The influence of a meal was reflecting strongly each weight of the heart, kidney, spleen, liver, and fat. Group A lower value indicates the average weight of the spleen when groups B, and A, were compared, statistically significant. Brain weight was not affected by diet and exercise