title: Minocycline protects oligodendroglial precursor cells against injury caused by oxygen-glucose deprivation.
abstract: Ischemic brain injury is widely modeled in vitro with paradigms of oxygen-glucose deprivation (OGD), which leads to cell death. The prevention and attenuation of brain injury by the tetracycline antibiotic minocycline has been attributed largely to suppression of microglial activation, but its benefits in oligodendrocyte cells have not been well characterized. Using primary cultures of rat oligodendroglial precursor cells (OPC) exposed to OGD, we investigated the direct effects of minocycline on the survival, proliferation, and maturation of oligodendroglial lineage cells. OGD for 2 hr caused a decrease in the total number of OPC and the amount of proliferating progenitors by 50%, which was attenuated by inclusion of minocycline. The reduced numbers of immature oligodendroglial cells at 72 hr and of mature oligodendrocytes at 120 hr after OGD were partially restored by minocycline. In OPC, OGD caused an increase of reactive oxygen species (ROS) and production of TUNEL-positive cell numbers, which was abolished by minocycline. Minocycline preferentially increased the expression of superoxide dismutase under OGD but not in control OPC. Minocycline also prevented the OGD-induced downregulation of the transcription factors Sox10 and Olig2 and of myelin-specific genes 2'3' cyclic nucleotide phosphodiesterase (CNP) and myelin basic protein (MBP) in response to OGD. These studies demonstrate direct protective actions of minocycline on oligodendroglial-lineage cells, suggesting potential benefit in white matter injury involving OGD.
authors.affiliation: Department for Neonatology, Charité University Medical Center, Berlin, Germany. thomas.schmitz@charite.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitz
authors.forename: Stefanie
authors.initials: S
authors.lastname: Endesfelder
authors.forename: Li-Jin
authors.initials: LJ
authors.lastname: Chew
authors.forename: Irina
authors.initials: I
authors.lastname: Zaak
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency*; D000860:Hypoxia / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000378:metabolism; D019081:O Antigens / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005732:Gangliosides; D019394:Ki-67 Antigen; D004676:Myelin Basic Protein; D019081:O Antigens; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors; C062875:ganglioside A2B5; C022616:thiazolyl blue; D008911:Minocycline; D005947:Glucose