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Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures.
Neurosci Lett 2015; 594:99-104NL

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+Show Affiliations

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.Department of Traumatology, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.Department of Neurosurgery, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.Department of Traumatology, AnNing Branch Hospital, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu Province 730070, China.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25827488

Citation

Gao, Chen, et al. "Monocarboxylate Transporter-dependent Mechanism Confers Resistance to Oxygen- and Glucose-deprivation Injury in Astrocyte-neuron Co-cultures." Neuroscience Letters, vol. 594, 2015, pp. 99-104.
Gao C, Zhou L, Zhu W, et al. Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures. Neurosci Lett. 2015;594:99-104.
Gao, C., Zhou, L., Zhu, W., Wang, H., Wang, R., He, Y., & Li, Z. (2015). Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures. Neuroscience Letters, 594, pp. 99-104. doi:10.1016/j.neulet.2015.03.062.
Gao C, et al. Monocarboxylate Transporter-dependent Mechanism Confers Resistance to Oxygen- and Glucose-deprivation Injury in Astrocyte-neuron Co-cultures. Neurosci Lett. 2015 May 6;594:99-104. PubMed PMID: 25827488.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures. AU - Gao,Chen, AU - Zhou,Liya, AU - Zhu,Wenxia, AU - Wang,Hongyun, AU - Wang,Ruijuan, AU - He,Yunfei, AU - Li,Zhiyun, Y1 - 2015/03/28/ PY - 2015/02/08/received PY - 2015/03/26/revised PY - 2015/03/27/accepted PY - 2015/4/2/entrez PY - 2015/4/2/pubmed PY - 2015/9/15/medline KW - Astrocyte KW - Co-culture KW - Glucose deprivation KW - Monocarboxylate transporters KW - Oxygen deprivation SP - 99 EP - 104 JF - Neuroscience letters JO - Neurosci. Lett. VL - 594 N2 - 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. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/25827488/Monocarboxylate_transporter_dependent_mechanism_confers_resistance_to_oxygen__and_glucose_deprivation_injury_in_astrocyte_neuron_co_cultures_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(15)00255-4 DB - PRIME DP - Unbound Medicine ER -