Study on the mechanism of quercetin promoting myelin regeneration in CPZ induced demyelinating mice model

Abstract

Objective To observe the effect of quercetin on myelin regeneration in desyelinating mice induced by cuprizone (CPZ). Methods A total of 50 C57BL/6J mice were randomly divided into normal control group, model group, low, medium and high dose quercetin groups, 10 mice in each group. In addition to the normal control group, mice demyelinating model was induced by feeding with 0.2% CPZ rodent feed. Quercetin solution was administered to the low, medium and high dose quercetin groups at 25, 50 and 100 mg/kg, and to the normal control group and the model group at 1 time/d. After 5 weeks of continuous gavage, the weight of mice was recorded every week, and the experiment of rotating bar was carried out. After 5 weeks, the changes of the myelin sheath in the corpus callosum of mice were observed by luxol fast blue (LFB) and transmission electron microscope (TEM). Immunofluorescence method was used to determine the protein expressions of myelin basic protein (MBP) and oligodendrocyte transcription 2actor (Olig2) in mouse brain tissue. The expression of MBP and cyclic nucleotide-3'phosphate hydrolase (CNPase) in mouse corpus callosum was determined by Western blot. Results After 2-5 weeks, compared with the model group, the body mass of the medium and high dose quercetin groups significantly increased (P<0.01), and the score of turning rod significantly increased (P<0.01). The LFB observation showed that the demyelination score of corpus callosum in low, medium and high dose quercetin groups (2.23 ± 0.25, 1.50 ± 0.15, 1.14 ± 0.97 vs. 2.83 ± 0.18) significantly decreased (P<0.01). TEM observation showed that the G-ratio value in low, medium and high dose quercetin groups (0.75 ± 0.05, 0.75 ± 0.08, 0.73 ± 0.08 vs. 0.87 ± 0.05) significantly reduced (P<0.01). Immunofluorescence observation showed that the positive expression of MBP (37.40 ± 2.41, 37.40 ± 1.14 vs. 24.40 ± 3.65) and Olig2 (7.40 ± 1.14, 4.60 ± 1.14 vs. 2.80 ± 0.84) in the medium and high dose quercetin groups significantly increased (P<0.05). WB showed that the expression of MBP protein (1.32 ± 0.12, 0.80 ± 0.34 vs. 0.21 ± 0.07) and CNPase protein (0.72 ± 0.13, 1.06 ± 0.36 vs. 0.36 ± 0.21) in the medium and high dose quercetin groups significantly increased (P<0.05). Conclusions Quercetin (50-100 mg/kg) can reduce myelin injury and promote myelin regeneration in CPZ mice, as a neuroprotective effect on CPZ mice. Key words: Quercetin; Multiple sclerosis; Demyelinating diseases; Remyelination; Oligodendrocyte precursor cells; Mice