Title : Targeting the activation of Microglia and M2-like shift in Multiple Sclerosis: from Mechanisms Study to Therapeutic intervention with Ganoderma Lucidum Spore Powder
Abstract:
Objective:
To investigate whether the Ganoderma Lucidum Spore (GLS) powder could alleviate the experimental autoimmune encephalomyelitis by attenuating the activation and polarization of microglia both in vivo and vitro.
Methods:
C57BL/6N female mice (~10 weeks, n=7 for each group) were induced by CFA and MOG35-55 with intravenous injection of Pertussis Toxin. Two treatment protocols were adopted: for pretreatment protocol, the GLS was orally administrated from day 2 to day 30 post-immunization, for the early prevention protocol, GLS was orally administrated 7 days before immunization until day 30 post-immunization. Daily assessment of body weight and clinical score were processed. Hematoxylin & Eosin (H&E), Luxol Fast Blue(LFB), Immunohistochemical (IHC) and immunofluorescence (IF) methods were applied to determine the inflammatory infiltration, demyelination, activation and polarization of microglia in mouse central nervous system. The Western Blot and qPCR were applied to elucidate the potential mechanism.
Result:
The result revealed that the GLP could alleviate experimental autoimmune encephalomyelitis (EAE) progression, delay the onset of EAE and reduce the severity of EAE. For the H&E and LFB results, GLP was indicated to reduce the inflammatory infiltration and demyelination in the spinal cord of EAE immunized mice (**p<0.01). The IHC and IF results indicated the activation of microglia and the M1/M2 ratio of microglia was significantly reduced (P<0.05). The inflammatory related cytokines such as IL-4, and IL-10 was reduced after GLS treatment. Besides, GLS was revealed to attenuate the microglial apoptosis, phagocytosis, and free radical generation to have beneficial effects.
Conclusions:
Overall, the GLP treatment could alleviate the EAE to indicate a potential therapeutic approach toward Multiple Sclerosis. GLP revealed to have a positive impact on immune modulation, neuroprotection, anti-apoptosis, and anti-oxidation via mediating the activation and polarization of microglia through attenuating NF-kB pathway.
