title: Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: implications for neurodegenerative diseases.
abstract: BACKGROUND
  Activated microglial cells are an important pathological component in brains of patients with neurodegenerative diseases. The purpose of this study was to investigate the effect of He-Ne (632.8 nm, 64.6 mW/cm2) low-level laser therapy (LLLT), a non-damaging physical therapy, on activated microglia, and the subsequent signaling events of LLLT-induced neuroprotective effects and phagocytic responses.
  
  
  METHODS
  To model microglial activation, we treated the microglial BV2 cells with lipopolysaccharide (LPS). For the LLLT-induced neuroprotective study, neuronal cells with activated microglial cells in a Transwell™ cell-culture system were used. For the phagocytosis study, fluorescence-labeled microspheres were added into the treated microglial cells to confirm the role of LLLT.
  
  
  RESULTS
  Our results showed that LLLT (20 J/cm2) could attenuate toll-like receptor (TLR)-mediated proinflammatory responses in microglia, characterized by down-regulation of proinflammatory cytokine expression and nitric oxide (NO) production. LLLT-triggered TLR signaling inhibition was achieved by activating tyrosine kinases Src and Syk, which led to MyD88 tyrosine phosphorylation, thus impairing MyD88-dependent proinflammatory signaling cascade. In addition, we found that Src activation could enhance Rac1 activity and F-actin accumulation that typify microglial phagocytic activity. We also found that Src/PI3K/Akt inhibitors prevented LLLT-stimulated Akt (Ser473 and Thr308) phosphorylation and blocked Rac1 activity and actin-based microglial phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway.
  
  
  CONCLUSIONS
  The present study underlines the importance of Src in suppressing inflammation and enhancing microglial phagocytic function in activated microglia during LLLT stimulation. We have identified a new and important neuroprotective signaling pathway that consists of regulation of microglial phagocytosis and inflammation under LLLT treatment. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, No, 55 Zhongshan Avenue West, Guangzhou, Tianhe District, 510631, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Song
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhou
authors.forename: Wei R
authors.initials: WR
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D028022:Low-Level Light Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000528:radiation effects*; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000528:radiation effects; D010590:Phalloidine / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013223:Statistics as Topic; D013997:Time Factors; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D002867:Chromones; D003497:Cyclic N-Oxides; D016207:Cytokines; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007093:Imidazoles; C549075:LY 290042; D008070:Lipopolysaccharides; D009025:Morpholines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010590:Phalloidine; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D020830:rac1 GTP-Binding Protein