PMID- 25827488 OWN - NLM STAT- MEDLINE DCOM- 20150914 LR - 20200325 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 594 DP - 2015 May 6 TI - Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures. PG - 99-104 LID - S0304-3940(15)00255-4 [pii] LID - 10.1016/j.neulet.2015.03.062 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Gao, Chen AU - Gao C AD - Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China. FAU - Zhou, Liya AU - Zhou L AD - Electrophysiology Examining Room, Department of Neurology, People's Hospital of Gansu Province, Lanzhou, Gansu Province 730000, China. FAU - Zhu, Wenxia AU - Zhu W AD - Department of Traumatology, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China. FAU - Wang, Hongyun AU - Wang H AD - Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China. FAU - Wang, Ruijuan AU - Wang R AD - Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China. FAU - He, Yunfei AU - He Y AD - Department of Traumatology, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China. FAU - Li, Zhiyun AU - Li Z AD - 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. LA - eng PT - Journal Article DEP - 20150328 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Antigens, Nuclear) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Monocarboxylic Acid Transporters) RN - 0 (Muscle Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Rbfox3 protein, rat) RN - 0 (Slc16a3 protein, rat) RN - 0 (Slc16a7 protein, rat) RN - 33X04XA5AT (Lactic Acid) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Antigens, Nuclear/metabolism MH - Astrocytes/cytology/drug effects/*metabolism MH - Cell Hypoxia MH - Cell Survival MH - Coculture Techniques MH - Embryo, Mammalian/cytology MH - Glial Fibrillary Acidic Protein/metabolism MH - Glucose/*deficiency MH - Hippocampus/cytology MH - Lactic Acid/pharmacology MH - Monocarboxylic Acid Transporters/genetics/*metabolism MH - Muscle Proteins/genetics/*metabolism MH - Nerve Tissue Proteins/metabolism MH - Neurons/cytology/drug effects/*metabolism MH - Oxygen/*metabolism MH - RNA Interference MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Astrocyte OT - Co-culture OT - Glucose deprivation OT - Monocarboxylate transporters OT - Oxygen deprivation EDAT- 2015/04/02 06:00 MHDA- 2015/09/15 06:00 CRDT- 2015/04/02 06:00 PHST- 2015/02/08 00:00 [received] PHST- 2015/03/26 00:00 [revised] PHST- 2015/03/27 00:00 [accepted] PHST- 2015/04/02 06:00 [entrez] PHST- 2015/04/02 06:00 [pubmed] PHST- 2015/09/15 06:00 [medline] AID - S0304-3940(15)00255-4 [pii] AID - 10.1016/j.neulet.2015.03.062 [doi] PST - ppublish SO - Neurosci Lett. 2015 May 6;594:99-104. doi: 10.1016/j.neulet.2015.03.062. Epub 2015 Mar 28.