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: Chen Gao, Liya Zhou, Wenxia Zhu, Hongyun Wang, Ruijuan Wang, Yunfei He, Zhiyun Li
• Journal: Neuroscience letters (Neurosci Lett) Vol. 594 Pg. 99-104 (May 06 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 25827488 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antigens, Nuclear
• Glial Fibrillary Acidic Protein
• Monocarboxylic Acid Transporters
• Muscle Proteins
• Nerve Tissue Proteins
• Rbfox3 protein, rat
• Slc16a3 protein, rat
• Slc16a7 protein, rat
• Lactic Acid
• Glucose
• Oxygen

Topics

• Animals
• Antigens, Nuclear (metabolism)
• Astrocytes (cytology, drug effects, metabolism)
• Cell Hypoxia
• Cell Survival
• Coculture Techniques
• Embryo, Mammalian (cytology)
• Glial Fibrillary Acidic Protein (metabolism)
• Glucose (deficiency)
• Hippocampus (cytology)
• Lactic Acid (pharmacology)
• Monocarboxylic Acid Transporters (genetics, metabolism)
• Muscle Proteins (genetics, metabolism)
• Nerve Tissue Proteins (metabolism)
• Neurons (cytology, drug effects, metabolism)
• Oxygen (metabolism)
• RNA Interference
• Rats, Sprague-Dawley