Ameliorative effects of Moringa on cuprizone-induced memory decline in rat model of multiple sclerosis / 대한해부학회지

Cuprizone is a neurotoxin with copper-chelating ability used in animal model of multiple sclerosis in which oxidative stress has been documented as one of the cascade in the pathogenesis. Moringa oleifera is a phytomedicinal plant with antioxidant and neuroprotective properties. This study aimed at evaluating the ameliorative capability of M. oleifera in cuprizone-induced behavioral and histopathological alterations in the prefrontal cortex and hippocampus of Wistar rats. Four groups of rats were treated with normal saline, cuprizone, M. oleifera and a combination of M. oleifera and cuprizone, for five weeks. The rats were subjected to Morris water maze and Y-maze to assess long and short-term memory respectively. The animals were sacrificed, and brain tissues were removed for histochemical and enzyme lysate immunosorbent assay for catalase, superoxide dismutase, and nitric oxide. Cuprizone significantly induced oxidative and nitrosative stress coupled with memory decline and cortico-hippocampal neuronal deficits; however, administration of M. oleifera significantly reversed the neuropathological deficits induced by cuprizone.

AATYK is a Novel Regulator of Oligodendrocyte Differentiation and Myelination / 神经科学通报·英文版

Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.

Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone model of multiple sclerosis

Multiple sclerosis [MS] is an immune-mediated demyelinating disease of the central nervous system [CNS]. Stem cell transplantation is a new therapeutic approach for demyelinating diseases such as MS which may promote remyelination. In this study, we evaluate the remyelinating potential of adipose mesenchymal stem cells [ADSCs] and their effect on neural cell composition in the corpus callosum in an experimental model of MS. This experimental study used adult male C57BL/6 mice. Cultured ADSCs were confirmed to be CD73[+], CD90[+], CD31[-],CD45[-], and labeled by PKH26. Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. At day 0 after cuprizone removal, mice were randomly divided into two groups: the ADSCs-transplanted group and the control vehicle group [received medium alone]. Some mice of the same age were fed with their normal diet to serve as healthy control group. Homing of ADSCs in demyelinated lesions was examined by fluorescent microscope. At ten days after transplantation, the mice were euthanized and their cells analyzed by luxol fast blue staining [LFB], transmission electron microscopy and flow cytometry. Results were analyzed by one-way analysis of variance [ANOVA]. According to fluorescent cell labeling, transplanted ADSCs appeared to survive and exhibited homing specificity. LFB staining and transmission electron microscope evaluation revealed enhanced remyelination in the transplanted group compared to the control vehicle group. Flow cytometry analysis showed an increase in Olig2 and O4 cells and a decrease in GFAP and Iba-1 cells in the transplanted group. Our results indicate that ADSCs may provide a feasible, practical way for remyelination in diseases such as MS

Immunochemical Study on the Changes of Carbonic anhydrase-II and Iron-binding Proteins in the Demyelinationand and Remyelination model Mouse induced with Cuprizone / 대한해부학회지

O1igodendrocytes are known to be responsible for the synthesis and maintenance of myelin sheath in the central nervous system, and their functional disturbance leads to defect in myelination. But, the fine mechanism of myelination by oligodendrocytes is not yet known, and iron metabolism in central nervous system is suspected to be related with myelination process by oligodendrocytes. Carbonic anhydrase-II[CA-II], transfe-rrin, and ferritin are known to be present at oligodendrocytes and suspected to play a role in iron metabolism of central nervous system. In this study, demyelination and remyelination of ICR mouse brains were induced using cuprizone, the copper-chelating agent, and immunohistochemical changes of CA-II-, transferrin-, and ferritin-immunoreactive oligodendrocytes at corpus callosum were observed. During demyelination by cuprizone feeding, the numbers of CA-II- and transferrin-immunoreactive oligodendrocytes were decreased. Especially, the decrease ratio of CA-II-positive cells was great. In contrast, the number of ferritin-positive oligodendrocytes was increased during demyelination by cuprizone feeding. Cessation of cuprizone feeding leaded remyelination and the numbers of CA-II-, transferrin-, and ferritin-immunoreactive oligodendrocytes were returned to normal level. In conclusion, the derangement of iron metabolism in oligodendrocytes may be related to demyelination mechanism of central nervous system, and the CA-II is suspected to have an important role in iron metabolism of oligodenrocytes in relation to demyelination and remyelination induced with cuprizone.