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Neurochemical Research

, Volume 42, Issue 10, pp 2881–2891 | Cite as

Ginkgolide B Suppresses Methamphetamine-Induced Microglial Activation Through TLR4-NF-κB Signaling Pathway in BV2 Cells

  • Fen Wan
  • Songsong Zang
  • Guoqing Yu
  • Hang Xiao
  • Jun WangEmail author
  • Jinrong TangEmail author
Original Paper

Abstract

Accumulating evidence suggests that microglial cells have altered morphology and proliferation in different brain regions of methamphetamine (Meth) abusers and Meth-abusing animal models. However, the possible mechanisms underlying Meth-induced microglial activation remain poorly understood. Meanwhile, Toll-like receptor4 (TLR4) is closely associated with inflammation. Therefore the aim of the present study was to assess whether Meth treatment affects TLR4 expression; in addition, we evaluated the effects of ginkgolide B (GB), a diterpene lactone extracted from Ginkgo biloba, on Meth-mediated inflammation. BV2 cells were treated with Meth. Interestingly, Meth treatment significantly increased TLR4 expression, activated the NF-κB signaling pathway, and promoted TNF-α, IL-6 and IL-1β excretion. These effects, however, were partially attenuated by GB pre-treatment. To further confirm the role of TLR4 in Meth-mediated inflammation, the siRNA technology was applied to knock down TLR4, which resulted in hampered Meth-mediated inflammatory responses, confirming the important role of TLR4 in this process. Taken together, our findings suggested that Meth exposure results in BV2 cell activation, in association with TLR4 upregulation. GB could attenuate Meth-induced inflammation, at least partially through TLR4-NF-κB signaling pathway, therefore, targeting TLR4 may constitute a potential intervention strategy for Meth mediated neuroinflammation.

Keywords

Methamphetamine Ginkgolide B BV2 cells TLR4 NF-κB 

Notes

Acknowledgements

This work was supported by the Natural Science Foundation of China (81202230, 81673213), the National Natural Science Foundation of Jiangsu Province (BK20151557), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Program for Key disease of Jiangsu Province Science and Technology Department (BL2014088).

Compliance with Ethical Standards

Conflict of interest

The authors did not report any conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of NeurologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public HealthNanjing Medical UniversityNanjingChina

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