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Minocycline protects oligodendroglial precursor cells against injury caused by oxygen‐glucose deprivation
Author(s) -
Schmitz Thomas,
Endesfelder Stefanie,
Chew LiJin,
Zaak Irina,
Bührer Christoph
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22824
Subject(s) - minocycline , neuroprotection , microglia , oligodendrocyte , reactive oxygen species , downregulation and upregulation , apoptosis , biology , myelin , pharmacology , myelin basic protein , chemistry , microbiology and biotechnology , immunology , biochemistry , inflammation , central nervous system , endocrinology , antibiotics , gene
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. © 2012 Wiley Periodicals, Inc.