Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures

• Published in: Neuroscience letters Vol. 594; pp. 99 - 104
• Main Authors: Gao, Chen, Zhou, Liya, Zhu, Wenxia, Wang, Hongyun, Wang, Ruijuan, He, Yunfei, Li, Zhiyun
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 06.05.2015
• Subjects: Animals; Antigens, Nuclear - metabolism; Astrocyte; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Cell Hypoxia; Cell Survival; Co-culture; Coculture Techniques; Embryo, Mammalian - cytology; Glial Fibrillary Acidic Protein - metabolism; Glucose - deficiency; Glucose deprivation; Hippocampus - cytology; Lactic Acid - pharmacology; Monocarboxylate transporters; Monocarboxylic Acid Transporters - genetics; Monocarboxylic Acid Transporters - metabolism; Muscle Proteins - genetics; Muscle Proteins - metabolism; Nerve Tissue Proteins - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Oxygen - metabolism; Oxygen deprivation; Rats, Sprague-Dawley; RNA Interference; DMEM/F12; Astrocyte; OGD; GFAP; SD; HIF-1; MTCs; Glucose deprivation; NeuN; Monocarboxylate transporters; FBS; RT-PCR; Oxygen deprivation; Co-culture
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2015.03.062

•8h OGD significantly increases cell death in primary neuronal cultures.•OGD up-regulates MCT4 expression in primary astrocyte cultures.•Neuronal cell death in co-cultures is increased by exposure to MCTs-specific siRNA under OGD.•Exogenous lactate in the extracellular medium can protect neuronal cultures from OGD. 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.