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Insulin‐like growth factor‐1 abrogates microglial oxidative stress and TNF ‐α responses to spreading depression
Author(s) -
Grinberg Yelena Y.,
Dibbern Megan E.,
Levasseur Victoria A.,
Kraig Richard P.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12267
Subject(s) - microglia , oxidative stress , tumor necrosis factor alpha , endocrinology , medicine , reactive oxygen species , cortical spreading depression , astrocyte , growth factor , hippocampal formation , insulin like growth factor , migraine , biology , chemistry , microbiology and biotechnology , receptor , central nervous system , inflammation
Spreading depression ( SD ), the most likely cause of migraine aura and perhaps migraine, occurs with increased oxidative stress ( OS ). SD increases reactive oxygen species ( ROS ), and ROS , in turn, can signal to increase neuronal excitability, which includes increased SD susceptibility. SD also elevates tumor necrosis factor‐α ( TNF ‐α), which increases neuronal excitability. Accordingly, we probed for the cellular origin of OS from SD and its relationship to TNF ‐α, which might promote SD , using rat hippocampal slice cultures. We observed significantly increased OS from SD in astrocytes and microglia but not in neurons or oligodendrocytes. Since insulin‐like growth factor‐1 ( IGF ‐1) mitigates OS from SD , we determined the cell types responsible for this effect. We found that IGF ‐1 significantly decreased microglial but not astrocytic OS from SD . We also show that IGF ‐1 abrogated the SD ‐induced TNF ‐α increase. Furthermore, TNF ‐α application increased microglial but not astrocytic OS , an effect abrogated by IGF ‐1. Next, we showed that SD increased SD susceptibility, and does so via TNF ‐α. This work suggests that microglia promote SD via increased and interrelated ROS and TNF ‐α signaling. Thus, IGF ‐1 mitigation of microglial ROS and TNF ‐α responses may be targets for novel therapeutics development to prevent SD , and perhaps migraine.Spreading depression (SD), the likely cause of migraine, occurs with increased TNF‐α and oxidative stress (OS), which we show is specific to microglia and astrocytes. We then show TNF‐α and SD itself increase susceptibility to subsequent SD. IGF‐1 decreases TNF‐α and microglial OS from SD. These findings support IGF‐1 and microglial OS as potential therapeutic targets against SD and perhaps migraine.