title: Methylene blue protects astrocytes against glucose oxygen deprivation by improving cellular respiration.
abstract: Astrocytes outnumber neurons and serve many metabolic and trophic functions in the mammalian brain. Preserving astrocytes is critical for normal brain function as well as for protecting the brain against various insults. Our previous studies have indicated that methylene blue (MB) functions as an alternative electron carrier and enhances brain metabolism. In addition, MB has been shown to be protective against neurodegeneration and brain injury. In the current study, we investigated the protective role of MB in astrocytes. Cell viability assays showed that MB treatment significantly protected primary astrocytes from oxygen-glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the effect of MB on cellular oxygen and glucose metabolism in primary astrocytes following OGD-reoxygenation injury. MB treatment significantly increased cellular oxygen consumption, glucose uptake and ATP production in primary astrocytes. In conclusion our study demonstrated that MB protects astrocytes against OGD-reoxygenation injury by improving astrocyte cellular respiration.
authors.affiliation: Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
authors.forename: Gourav
authors.initials: G
authors.lastname: Roy Choudhury
authors.affiliation: Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Winters
authors.affiliation: Department of Cell Biology & Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Rich
authors.affiliation: Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
authors.forename: Myoung-Gwi
authors.initials: MG
authors.lastname: Ryou
authors.affiliation: Department of Cell Biology & Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Gryczynski
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Texas, United States of America; Department of Neurosurgery, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia; D019069:Cell Respiration / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D019610:Cytoprotection; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006593:Hexokinase / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption
chemical_list: D018696:Neuroprotective Agents; D000255:Adenosine Triphosphate; D006003:Glycogen; D006593:Hexokinase; D005947:Glucose; D010100:Oxygen; D008751:Methylene Blue
references.citation: J Neurosci Res. 2005 Jan 1-15;79(1-2):74-80
references.pmid: 15578727
references.citation: Free Radic Biol Med. 2005 Jun 1;38(11):1433-44
references.pmid: 15890617
references.citation: Neurotox Res. 2006 Jan;9(1):47-57
references.pmid: 16464752
references.citation: Nat Rev Neurosci. 2006 Mar;7(3):194-206
references.pmid: 16495941
references.citation: J Neurosci. 2006 Mar 15;26(11):2862-70
references.pmid: 16540563
references.citation: Neurochem Int. 2006 May-Jun;48(6-7):531-40
references.pmid: 16504342
references.citation: J Neurochem. 2006 May;97(4):968-78
references.pmid: 16606370
references.citation: Nat Clin Pract Neurol. 2006 Dec;2(12):679-89
references.pmid: 17117171
references.citation: Mol Interv. 2008 Dec;8(6):268-73
references.pmid: 19144897
references.citation: Biochem Pharmacol. 2009 Oct 15;78(8):927-32
references.pmid: 19433072
references.citation: J Neurochem. 2002 Mar;80(5):780-7
references.pmid: 11948241
references.citation: J Biomed Opt. 2002 Jul;7(3):404-9
references.pmid: 12175290
references.citation: J Biol Chem. 2003 Sep 19;278(38):36027-31
references.pmid: 12840017
references.citation: Trends Neurosci. 2003 Oct;26(10):523-30
references.pmid: 14522144
references.citation: J Cereb Blood Flow Metab. 2004 Sep;24(9):1004-14
references.pmid: 15356421
references.citation: Cell. 2004 Sep 17;118(6):665-6
references.pmid: 15369664
references.citation: J Cereb Blood Flow Metab. 1981;1(3):297-311
references.pmid: 7328145
references.citation: Proc Natl Acad Sci U S A. 1990 Jul;87(13):5144-7
references.pmid: 1973301
references.citation: Brain Res. 1991 Jul 19;554(1-2):186-92
references.pmid: 1657286
references.citation: Stroke. 1996 Jun;27(6):1124-9
references.pmid: 8650725
references.citation: J Cereb Blood Flow Metab. 1997 Oct;17(10):1048-56
references.pmid: 9346429
references.citation: Trends Neurosci. 1999 Sep;22(9):391-7
references.pmid: 10441299
references.citation: Metab Brain Dis. 2004 Dec;19(3-4):151-67
references.pmid: 15554412
references.citation: Biochim Biophys Acta. 2010 Jan;1802(1):80-91
references.pmid: 19751827
references.citation: Neurology. 2010 Mar 16;74(11):919-23
references.pmid: 20231669
references.citation: Lancet Neurol. 2011 Feb;10(2):187-98
references.pmid: 21147038
references.citation: Stroke. 2011 May;42(5):1495-9
references.pmid: 21474803
references.citation: J Biol Chem. 2011 May 6;286(18):16504-15
references.pmid: 21454572
references.citation: Neuron. 2011 Sep 8;71(5):782-97
references.pmid: 21903073
references.citation: Cell Metab. 2011 Dec 7;14(6):724-38
references.pmid: 22152301
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):E2334-42
references.pmid: 22826245
references.citation: PLoS One. 2012;7(10):e46585
references.pmid: 23056355
references.citation: PLoS One. 2012;7(10):e48279
references.pmid: 23118969
references.citation: Mol Neurobiol. 2013 Feb;47(1):9-23
references.pmid: 23011809
references.citation: J Biol Chem. 2013 Mar 29;288(13):9153-64
references.pmid: 23408428
references.citation: PLoS One. 2013;8(11):e79833
references.pmid: 24278191
references.citation: Brain Res. 2014 Mar 10;1551:45-58
references.pmid: 24440774
references.citation: J Neurotrauma. 2014 Jun 1;31(11):1063-71
references.pmid: 24479842
references.citation: Hum Mol Genet. 2014 Jul 15;23(14):3716-32
references.pmid: 24556215
references.citation: Brain Res. 2014 Nov 7;1588:144-9
references.pmid: 25218555
references.citation: J Cereb Blood Flow Metab. 1992 Mar;12(2):193-203
references.pmid: 1548292
references.citation: Can J Physiol Pharmacol. 1992;70 Suppl:S138-44
references.pmid: 1295664
references.citation: Arch Neurol. 2007 Apr;64(4):507-13
references.pmid: 17296829
references.citation: Pharmacol Biochem Behav. 2007 May;87(1):179-97
references.pmid: 17521716
references.citation: Glia. 2007 Sep;55(12):1263-71
references.pmid: 17659525
references.citation: FASEB J. 2008 Mar;22(3):703-12
references.pmid: 17928358
references.citation: Stroke. 2008 Jun;39(6):1751-8
references.pmid: 18369171