RESUMO
A growing body of studies suggests that Ca2+ signaling controls a variety of biological processes in brain elements. Activation of L-type voltage-operated Ca2+ channels (VOCCs) plays a role in the development of oligodendrocyte (OL) lineage loss, and indicates that the blocking of these channels may be an effective way to inhibit OL lineage cell loss. For this study, 10.5-day-old male Sprague-Dawley rats were used to generate cerebellar tissue slices. The slice tissues were cultured and randomly allocated to one of four groups (six each) and treated as follows: Group I, (sham control); Group II, 0.1% dimethyl sulfoxide (DMSO) only (vehicle control); Group III, injury (INJ); Group IV, (INJ and treatment with NIF). The injury was simulated by exposing the slice tissues to 20 min of oxygen-glucose deprivation (OGD). At 3 days post-treatment, the survival, apoptosis, and proliferation of the OL lineages were measured and compared. Results: In the INJ group, there was a decrease in mature myelin basic protein+ OLs (MBP+ OLs) and their precursors, NG2+ OPCs (Nerve-glia antigen 2+ oligodendrocyte precursor cell), compared with controls. A significant elevation was observed in the NG2+ OPCs and apoptotic MBP+ OLs as confirmed by a TUNEL assay. However, the cell proliferation rate was decreased in NG2+ OPCs. NIF increased OL survival as measured by apoptosis rate in both OL lineages and preserved the rate of proliferation in the NG2+ OPCs. Conclusions: Activation of L-type VOCCs may contribute to OL pathology in association with reduced mitosis of OPCs following brain injury as a strategy to treat demyelinating diseases.
RESUMO
Background: During early life, exposure to environmental toxicants, including endocrine disruptor bisphenol A (BPA), can be detrimental to the immune system. To our knowledge, a few researches have looked at the effects of developing BPA exposures on the spleen. Aim: The murine model was developed to investigate the underlying molecular mechanisms and mode of BPA actions on the spleen subsequent to prolonged early-life exposure to BPA. Methods: Immature (3-week-old) male and female Swiss Albino mice were intraperitoneally injected with 50 µg/kg BPA in corn oil or corn oil alone for 6 weeks. Mouse spleens were harvested and examined histologically at 10 weeks old (adulthood). Results: We observed neurobehavioral impairments and a significant increase in peripheral monocyte and lymphocyte counts in mice (males and females). Moreover, several spleen abnormalities in both male and female mice were observed in adulthood. BPA-treated mice's histopathological results revealed toxicity in the form of significantly active germinal centers of the white pulp and a few apoptotic cells. There was also a notable invasion of the red pulp by eosinophils and lymphocytes that were significantly higher than normal. Agarose gel electrophoresis provided further evidence of internucleosomal DNA fragmentation and apoptosis in the splenic tissues of BPA-treated mice compared to controls. In addition, there were increased levels of the lipid peroxidation malondialdehyde end-product, a marker of oxidative lipid damage, in the spleens of BPA-treated mice compared to controls. Conclusion: Our study provides evidence that oxidative stress injury induced by early-life exposures to BPA could contribute to a range of splenic tissue damages during adulthood.