Salvianolic acid B promotes microglial M2-polarization and rescues neurogenesis in stress-exposed mice

• Published in: Brain, behavior, and immunity behavior, and immunity, 2017-11, Vol.66, p.111-124
• Main Authors: Zhang, Jinqiang, Xie, Xiaofang, Tang, Mingming, Zhang, Jing, Zhang, Boyang, Zhao, Qiuying, Han, Yue, Yan, Wan, Peng, Cheng, You, Zili
• Format: Article
• Language: English
• Subjects: Animals; Benzofurans - administration & dosage; Cerebral Cortex - drug effects; Cerebral Cortex - physiopathology; Cytokine; Depression; Depression - complications; Depression - physiopathology; Depression - prevention & control; Depressive Disorder - complications; Depressive Disorder - physiopathology; Depressive Disorder - prevention & control; Hippocampus - drug effects; Hippocampus - physiopathology; Inflammation - complications; Inflammation - metabolism; Inflammation Mediators - metabolism; Male; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - metabolism; Microglia - physiology; Neurogenesis; Neurogenesis - drug effects; Phenotype; Salvianolic acid B; Stress, Psychological - complications; Stress, Psychological - physiopathology
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2017.07.012

•CMS-induced M1 microglia contribute to neuroinflammatory and inhibit neurogenesis.•SalB rebalances the dysregulation of cytokines by regulating microglial phenotype.•M2 microglia reversed the CMS-induced deficits in neurogenesis and behaviors.•Targeting microglial phenotypes may represent a new strategy for depression therapy. Although accumulating evidence suggests that activated microglia are associated with deficits in neurogenesis and contribute to the physiopathology of major depressive disorder, the role of microglia in treating depression remains poorly understood. Our previous study showed that salvianolic acid (SalB) has the regulation of neuroinflammatory responses and antidepressant-like effects. Here, we hypothesized that SalB’s therapeutic effects occur because it modulates microglial phenotypes that are associated with neurogenesis. To test this hypothesis, we treated CMS-exposed C57BL/6 mice with SalB (20mg/kg, intraperitoneally, once daily) for 3weeks and investigated microglial phenotypic profiles and hippocampal neurogenesis. The results showed that the SalB treatment skewed M1 microglial polarization toward M2 activation in the hippocampus and cortex and remedied CMS-induced deficits in hippocampal neurogenesis. SalB (40µM) inhibited LPS-stimulated microglial M1 activation as well as induced M2 activation in vitro, and the cultured microglia with the SalB treatment showed enhanced neural precursor cell proliferation, differentiation, and survival. SalB treatment also ameliorated the depressive-like behaviors of the CMS-treated mice in sucrose preference, forced swimming, and tail suspension tests. These findings suggest a possible antidepressive mechanism for anti-inflammatory agents that is correlated with microglial polarization and hippocampal neurogenesis and which may provide a new microglia-targeted strategy for depression therapy.