Peroxisome proliferator-activated receptor gamma participates in the acquisition of brain ischemic tolerance induced by ischemic preconditioning via glial glutamate transporter 1 in vivo and in vitro.
Peroxisome proliferator-activated receptor gamma participates in the acquisition of brain ischemic tolerance induced by ischemic preconditioning via glial glutamate transporter 1 in vivo and in vitro.
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过氧化物酶体增殖物激活受体 γ 在体内和体外参与通过神经胶质谷氨酸转运蛋白 1 进行缺血预处理诱导的脑缺血耐受的获得。
DOI：
10.1111/jnc.14824
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Zhang M
中科院分区：
文献类型：
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作者：
Zhao CC;Jiang MY;Zhang LY;Hu YY;Hu ZJ;Zhang MY;Qi J;Su AC;Lou N;Xian XH;Zhang JG;Li WB;Zhang M
胶质细胞谷氨酸转运体1(GLT-1)在脑缺血预适应(IPC)诱导脑缺血耐受(BIT)中起重要作用。然而，其机制仍需进一步解释。本研究的目的是探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)是否参与了IPC诱导的BIT获得过程中GLT-1的调节。最初，脑缺血预适应可诱导大鼠脑缺血再灌注损伤，并增强大鼠海马区PPARγ和GLT-1的表达。胞核/胞浆PPARγ比值升高。同时，PPARγ和胶质纤维酸性蛋白的双重免疫荧光显示，PPARγ在CA1区星形胶质细胞中表达上调。然后，在大鼠皮质星形胶质细胞-神经元共培养中，研究了PPARγ调节GLT-1的机制。我们发现，IPC[45h的氧糖剥夺(OGD)]保护了致死性OGD(4h的OGD)后的神经元存活，这通常会导致神经元死亡。免疫印迹和免疫荧光检测显示，缺血预适应后星形胶质细胞中PPARγ的激活早于GLT-1的上调。此外，预先给予PPARγ拮抗剂T0070907或PPARGLT-1 siRNA可显著减弱IPCin诱导的γ上调和神经保护作用。最后，在体内验证了PPARγ拮抗剂对GLT-1表达和BIT的影响。我们观察到，脑室注射T0070907可剂量依赖性地减弱大鼠脑缺血预适应引起的GLT-1和BIT的上调。总之，在Ipc诱导的BIT获取过程中，PPARjnc.jpar参与了对Glt-1的调节。有关此问题的图片：doi：10.1111/https://cos.io/our-services/open-science-badges/。开放科学：本手稿荣获开放材料奖有关更多信息，请访问：γ
Glial glutamate transporter 1 (GLT‐1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further explained. The aim of this study was to investigate whether peroxisome proliferator‐activated receptor gamma (PPARγ) participates in regulating GLT‐1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPARγ and GLT‐1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPARγ was also increased. At the same time, the up‐regulation of PPARγ expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPARγ and glial fibrillary acidic protein. Then, the mechanism by which PPARγ regulates GLT‐1 was studied in rat cortical astrocyte‐neuron cocultures. We found that IPC [45 min of oxygen glucose deprivation (OGD)] protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPARγ occurred earlier than the up‐regulation of GLT‐1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPARγ antagonist T0070907 or PPARγ siRNA significantly attenuated GLT‐1 up‐regulation and the neuroprotective effects induced by IPCin vitro. Finally, the effect of the PPARγ antagonist on GLT‐1 expression and BIT was verifiedin vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose‐dependently attenuated the up‐regulation of GLT‐1 and BIT induced by cerebral IPC in rats. In conclusion, PPARγ participates in regulating GLT‐1 during the acquisition of BIT induced by IPC.Cover Image for this issue: doi: 10.1111/jnc.14532.Open Science: This manuscript was awarded with the Open Materials BadgeFor more information see: https://cos.io/our-services/open-science-badges/