The protective role of proton-sensing TDAG8 in the brain injury in a mouse ischemia reperfusion model.
The protective role of proton-sensing TDAG8 in the brain injury in a mouse ischemia reperfusion model.
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质子感受型TDAG8对小鼠脑缺血再灌注损伤的保护作用
DOI：
10.1038/s41598-020-74372-7
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发表时间：
2020-10-14
影响因子：
4.6
通讯作者：
Okajima F
中科院分区：
文献类型：
--
作者：
Sato K;Tobo A;Mogi C;Tobo M;Yamane N;Tosaka M;Tomura H;Im DS;Okajima F
在缺血中已经观察到脑中的细胞外酸化;然而，pH值降低的生理和病理生理学意义在很大程度上仍然未知。在这里，我们分析了质子敏感G蛋白偶联受体，包括T细胞死亡相关基因8（TDAG 8），卵巢癌G蛋白偶联受体1（OGR 1），和G蛋白偶联受体4（GPR 4）在小鼠缺血再灌注模型中的作用。脑梗死和短暂性大脑中动脉闭塞（tMCAO）和随后的再灌注功能障碍的行为加剧了TDAG 8的缺陷，而没有观察到与OGR 1或GPR 4的缺陷的显着影响。我们证实，预测的梗死区域的pH值为6.5。在小鼠脑中的Iba 1阳性小胶质细胞中观察到TDAG 8 mRNA。tMCAO增加了同侧大脑半球肿瘤坏死因子-α mRNA的表达，并诱发了进展性脑损伤中小胶质细胞的形态学变化。这些tMCAO诱导的行动显着增强TDAG 8缺陷。二甲胺四环素，这是已知的抑制小胶质细胞活化，改善脑梗死和功能障碍的行为诱导的tMCAO在TDAG 8缺陷小鼠。因此，酸性pH/TDAG 8保护免受由tMCAO引起的脑梗死，至少是由于涉及抑制小胶质细胞功能的机制。
Extracellular acidification in the brain has been observed in ischemia; however, the physiological and pathophysiological implications of the pH reduction remain largely unknown. Here, we analyzed the roles of proton-sensing G protein-coupled receptors, including T-cell death-associated gene 8 (TDAG8), ovarian cancer G protein-coupled receptor 1 (OGR1), and G protein-coupled receptor 4 (GPR4) in a mouse ischemia reperfusion model. Cerebral infarction and dysfunctional behavior with transient middle cerebral artery occlusion (tMCAO) and subsequent reperfusion were exacerbated by the deficiency of TDAG8, whereas no significant effect was observed with the deficiency of OGR1 or GPR4. We confirmed that the pH of the predicted infarction region was 6.5. TDAG8 mRNA was observed in Iba1-positive microglia in the mouse brain. The tMCAO increased the mRNA expression of tumor necrosis factor-α in the ipsilateral cerebral hemisphere and evoked morphological changes in microglia in an evolving cerebral injury. These tMCAO-induced actions were significantly enhanced by the TDAG8 deficiency. Administration of minocycline, which is known to inhibit microglial activation, improved the cerebral infarction and dysfunctional behavior induced by tMCAO in the TDAG8-deficient mouse. Thus, acidic pH/TDAG8 protects against cerebral infarction caused by tMCAO, at least due to the mechanism involving the inhibition of microglial functions.
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影响因子：
4.6
作者：
Aoki H;Mogi C;Okajima F
通讯作者：
Okajima F
影响因子：
5.3
作者：
Iosif, Robert E.;Ekdahl, Christine T.;Lindvall, Olle
通讯作者：
Lindvall, Olle
白介素1α的表达在缺血性脑损伤后先于IL-1β，并定位于局灶性神经元丧失和半月组织。
影响因子：
9.3
作者：
Luheshi NM;Kovács KJ;Lopez-Castejon G;Brough D;Denes A
通讯作者：
Denes A
影响因子：
4.8
作者：
Jiang, SX;Lertvorachon, J;Preston, E
通讯作者：
Preston, E
影响因子：
4.4
作者：
Mogi, Chihiro;Tobo, Masayuki;Okajima, Fumikazu
通讯作者：
Okajima, Fumikazu