title: Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures.
abstract: 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.
authors.affiliation: Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.affiliation: Electrophysiology Examining Room, Department of Neurology, People's Hospital of Gansu Province, Lanzhou, Gansu Province 730000, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Traumatology, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Traumatology, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command, PLA, South of Binhe Road, No. 333, Lanzhou, Gansu Province 730050, China. Electronic address: Lizhiyun890@163.com.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015687:Cell Hypoxia; D002470:Cell Survival; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000166:cytology; D019344:Lactic Acid / Q000494:pharmacology; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley
chemical_list: D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; C516342:Slc16a3 protein, rat; C091633:Slc16a7 protein, rat; D019344:Lactic Acid; D005947:Glucose; D010100:Oxygen
keywords: Astrocyte; Co-culture; Glucose deprivation; Monocarboxylate transporters; Oxygen deprivation