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.
Animals ; Brain ; Carbon* ; Central Nervous System ; Corpus Callosum ; Cuprizone* ; Demyelinating Diseases ; Ferritins ; Iron ; Iron-Binding Proteins* ; Metabolism ; Mice* ; Mice, Inbred ICR ; Myelin Sheath ; Oligodendroglia ; Transferrin

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.
Animals ; Brain ; Catalase ; Cuprizone ; Hippocampus ; Memory* ; Memory, Short-Term ; Models, Animal* ; Moringa oleifera ; Moringa* ; Multiple Sclerosis* ; Neurons ; Nitric Oxide ; Oxidative Stress ; Plants ; Prefrontal Cortex ; Rats* ; Rats, Wistar ; Superoxide Dismutase ; Water

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.
Animals ; Animals, Newborn ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Cell Differentiation ; drug effects ; physiology ; Cell Proliferation ; drug effects ; genetics ; Cells, Cultured ; Cuprizone ; toxicity ; Demyelinating Diseases ; chemically induced ; metabolism ; pathology ; Embryo, Mammalian ; Gene Expression Regulation, Developmental ; genetics ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Inbred C57BL ; Myelin Basic Protein ; metabolism ; Myelin Proteolipid Protein ; metabolism ; Myelin Sheath ; drug effects ; metabolism ; Oligodendroglia ; drug effects ; metabolism ; Protein-Tyrosine Kinases ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley