Gao Chen, Zhou Liya, Zhu Wenxia, Wang Hongyun, Wang Ruijuan, He Yunfei, Li Zhiyun
Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.
Electrophysiology Examining Room, Department of Neurology, People's Hospital of Gansu Province, Lanzhou, Gansu Province 730000, China.
Neurosci Lett. 2015 May 6;594:99-104. doi: 10.1016/j.neulet.2015.03.062. Epub 2015 Mar 28.
Hypoxic and low-glucose stressors contribute to neuronal death in many brain diseases. Astrocytes are anatomically well-positioned to shield neurons from hypoxic injury. During hypoxia/ischemia, lactate released from astrocytes is taken up by neurons and stored for energy. This process is mediated by monocarboxylate transporters (MCTs) in the central nervous system. In the present study, we investigated the ability of astrocytes to protect neurons from oxygen- and glucose-deprivation (OGD) injury via an MCT-dependent mechanism in vitro. Primary cultures of neurons, astrocytes, and astrocytes-neurons derived from rat hippocampus were subjected to OGD, MCT inhibition with small interfering (si)RNA. Cell survival and expression of MCT4, MCT2, glial fibrillary acidic protein, and neuronal nuclear antigen were evaluated. OGD significantly increased cell death in neuronal cultures and up-regulated MCT4 expression in astrocyte cultures, but no increased cell death was observed in neuron-astrocyte co-cultures or astrocyte cultures. However, neuronal cell death in co-cultures was increased by exposure to MCT4- or MCT2-specific siRNA, and this effect was attenuated by the addition of lactate into the extracellular medium of neuronal cultures prior to OGD. These findings demonstrate that resistance to OGD injury in astrocyte-neuron co-cultures occurs via an MCT-dependent mechanism.
缺氧和低糖应激因素在许多脑部疾病中会导致神经元死亡。星形胶质细胞在解剖学上位置优越，能够保护神经元免受缺氧损伤。在缺氧/缺血期间，星形胶质细胞释放的乳酸被神经元摄取并储存以供能。这一过程由中枢神经系统中的单羧酸转运体（MCTs）介导。在本研究中，我们在体外研究了星形胶质细胞通过依赖MCT的机制保护神经元免受氧糖剥夺（OGD）损伤的能力。将源自大鼠海马体的神经元、星形胶质细胞以及神经元-星形胶质细胞原代培养物进行OGD处理，并用小干扰（si）RNA抑制MCT。评估细胞存活率以及MCT4、MCT2、胶质纤维酸性蛋白和神经元核抗原的表达。OGD显著增加了神经元培养物中的细胞死亡，并上调了星形胶质细胞培养物中MCT4的表达，但在神经元-星形胶质细胞共培养物或星形胶质细胞培养物中未观察到细胞死亡增加。然而，共培养物中的神经元细胞死亡因暴露于MCT4或MCT2特异性siRNA而增加，并且在OGD之前向神经元培养物的细胞外培养基中添加乳酸可减弱这种作用。这些发现表明，星形胶质细胞-神经元共培养物对OGD损伤的抗性是通过依赖MCT的机制发生的。
