Journal
NEUROTOXICITY RESEARCH
Volume 29, Issue 4, Pages 447-459Publisher
SPRINGER
DOI: 10.1007/s12640-015-9592-2
Keywords
Parkinson's disease; Doxycycline; Microglia; Cytokines
Categories
Funding
- MINCyTECOS Program [A12S02]
- (Center for Research in Inflammatory Disease) [2013/08216-2]
- Program Investissements d'avenir [ANR-10-IAIHU-06]
- Translational Research Infrastructure for Biotherapies in Neurosciences [ANR-11-INBS-0011-NeurATRIS]
- Science Without Borders CNPq Program
- Bernardo Houssay Program
- MINCyT-CONICET- CAMPUS FRANCE
- Sao Paulo Research Foundation (FAPESP) [2011/19670-0]
- CNPq
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In neurodegenerative diseases, the inflammatory response is mediated by activated glial cells, mainly microglia, which are the resident immune cells of the central nervous system. Activated microglial cells release proinflammatory mediators and neurotoxic factors that are suspected to cause or exacerbate these diseases. We recently demonstrated that doxycycline protects substantia nigra dopaminergic neurons in an animal model of Parkinson's disease. This effect was associated with a reduction of microglial cell activation, which suggests that doxycycline may operate primarily as an anti-inflammatory drug. In the present study, we assessed the anti-inflammatory potential of doxycycline using lipopolysaccharide (LPS)-activated primary microglial cells in culture as a model of neuroinflammation. Doxycycline attenuated the expression of key activation markers in LPS-treated microglial cultures in a concentration-dependent manner. More specifically, doxycycline treatment lowered the expression of the microglial activation marker IBA-1 as well as the production of ROS, NO, and proinflammatory cytokines (TNF-alpha and IL-1 beta). In primary microglial cells, we also found that doxycycline inhibits LPS-induced p38 MAP kinase phosphorylation and NF-kB nuclear translocation. The present results indicate that the effect of doxycycline on LPS-induced microglial activation probably occurs via the modulation of p38 MAP kinase and NF-kB signaling pathways. These results support the idea that doxycycline may be useful in preventing or slowing the progression of PD and other neurodegenerative diseases that exhibit altered glia function.
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