ABSTRACT
In multiple sclerosis patients, long-term inflammation makes the oligodendrocyte progenitor cells (OPCs) exhausted; therefore, a new therapy that makes them responsive to insults to participate in remyelination is highly in demand. Here, we investigated the effect of ursolic acid (UA) on myelin repair after mid-term and long-term demyelination periods induced by 6 or 12 weeks of cuprizone treatment followed by 2 weeks of recovery with or without UA. Immunohistochemistry studies and myelin genes expression assessment were used to evaluate the myelination status of mouse corpora callosa and the cellular mechanisms of myelin repair. Results showed that UA significantly promoted recovery from myelin loss after discontinuing 6 or 12 weeks of cuprizone feeding, as measured by luxol fast blue (LFB), fluoroMyelin (FM), anti-myelin basic protein (MBP) staining, and oligodendrocyte progenitor cell counts. It led to reduced inflammation and gliosis as evaluated by glial fibrillary acidic protein (GFAP), Iba1, or other marker gene transcripts. Following long-term demyelination, gliosis and TNF-α were observed as potential players in lesion pathology, which were restored by UA. An increased IL-10 may contribute to UA anti-inflammatory effect and making responsive the exhausted OPCs. UA increased the number of new oligodendrocyte lineage cells and myelination. Our findings indicated that UA can enhance myelin repair after cuprizone challenge through the prevention of gliosis and increasing the newly generated myelin.
Subject(s)
Demyelinating Diseases , Oligodendrocyte Precursor Cells , Animals , Mice , Cuprizone/toxicity , Oligodendrocyte Precursor Cells/metabolism , Glial Fibrillary Acidic Protein/metabolism , Interleukin-10/metabolism , Demyelinating Diseases/chemically induced , Demyelinating Diseases/drug therapy , Demyelinating Diseases/metabolism , Gliosis , Tumor Necrosis Factor-alpha/metabolism , Myelin Sheath/metabolism , Oligodendroglia/metabolism , Corpus Callosum/pathology , Inflammation/metabolism , Anti-Inflammatory Agents/pharmacology , Mice, Inbred C57BL , Disease Models, Animal , Ursolic AcidABSTRACT
Neuronal survival in multiple sclerosis (MS) and other demyelinating diseases depends on the preservation of myelin and remyelination of axons. Myelin protection is the main purpose to decrease myelin damage in the central nervous system (CNS). Ursolic acid (UA) as a natural product in apple is suggested to protect neural cells. This study is the first to demonstrate an effect for UA on CNS myelin loss induced by cuprizone toxin. In the current study, we hypothesized that daily treatment with UA in drinking water (1 mg/mL) prevents myelin damage by 6 weeks administration of CPZ in mice pellet which lead to corpus callosum axonal demyelination. We assessed the myelin content and the number of myelinating cells in corpus callosum by FluoroMyelin and luxol fast blue staining as well as by immunostaining against MBP and Olig2. Our finding indicated that UA could decrease the extent of demyelination area and enhanced myelin stain intensity within CC and protected oligodendrocyte lineage cells against cuprizone toxin. We could conclude that myelinated structures could be protected by UA in corpus callosum, which provide favorable evidence for the possibility of application of UA in demyelinating diseases and traumatic injuries.
ABSTRACT
BACKGROUND: Urban family physician program has been launched as a pilot in Fars and Mazandaran provinces of Iran since 2012. Attitudes of policy makers and people toward urban family physician program have become challenging. This study shows what people know and practice toward this program. METHODS: This cross-sectional population-based study was conducted by a multistage randomized sampling in Shiraz, Southern Iran. Knowledge and practice of adults toward urban family physician program were queried through filing the questionnaires. Single and multiple variable analyzes of data were performed. RESULTS: Participation rate was 1257 of 1382 (90.9%), and the mean age of the respondents was 38.1 ± 13.2 years. Of 1257, 634 (50.4%) were men and 882 (70.2%) were married. Peoples' total knowledge toward urban family physician program was 5 ± 2.7 of 19, showed that 1121 (89.2%) had a low level of knowledge. This was correlated positively and in order to being under coverage of this program (P < 0.001), being under coverage of one of the main insurance systems (P = 0.04) and being married (P = 0.002). The mean score of people's practice toward the program was 2.3 ± 0.9 of total score 7, showed that 942 (74%) had poor performance, and it was correlated positively and in order to being under coverage of this program (P < 0.001) and having higher than 1000$ monthly income (P = 0.004). Correlation of people's knowledge and practice toward the program was 24%. CONCLUSIONS: Current evidences show a low level of knowledge, poor practice and weak correlation of knowledge-practice of people toward urban family physician program.