• Molecules and Cells
• /
• v.38 no.11
• /
• pp.1013-1021
• /
• 2015

Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immune-modulating drug that is used in rheumatology and inflammatory bowel disease. Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS.

• Journal of Veterinary Science
• /
• v.19 no.6
• /
• pp.750-758
• /
• 2018

Influenza virus infection is a zoonosis that has great socioeconomic effects worldwide. Influenza infection induces respiratory symptoms, while the influenza virus can infect brain and leave central nervous system sequelae. As children are more vulnerable to infection, they are at risk of long-term neurological effects once their brains are infected. We previously demonstrated that functional changes in hippocampal neurons were observed in mice recovered from neonatal influenza infection. In this study, we investigated changes in myelination properties that could affect neural dysfunction. Mice were infected with the influenza virus on postnatal day 5. Tissues were harvested from recovered mice 21-days post-infection. The expression levels for myelin basic protein (MBP) were determined, and immunohistochemical staining and transmission electron microscopy were performed. Real-time polymerase chain reaction and Western blot analyses showed that mRNA and protein expressions increased in the hippocampus and cerebellum of recovered mice. Increased MBP-staining signal was observed in the recovered mouse brain. By calculating the relative thickness of myelin sheath in relation to nerve fiber diameter (G-ratio) from electron photomicrographs, an increased G-ratio was observed in both the hippocampus and cerebellum of recovered mice. Influenza infection in oligodendrocyte-enriched primary brain cell cultures showed that proinflammatory cytokines may induce MBP upregulation. These results suggested that increased MBP expression could be a compensatory change related to hypomyelination, which may underlie neural dysfunction in recovered mice. In summary, the present results demonstrate that influenza infection during the neonatal period affects myelination and further induces functional changes in influenza-recovered mouse brain.

• Journal of Ginseng Research
• /
• v.46 no.1
• /
• pp.104-114
• /
• 2022

Background: Abnormalities of myelin, which increases the efficiency of action potential conduction, are found in neurological disorders. Korean Red Ginseng (KRG) demonstrates therapeutic efficacy against some of these conditions, however effects on oligodendrocyte (OL)s are not well known. Here, we examined the effects of KRG-derived components on development and protection of OL-lineage cells. Methods: Primary OL precursor cell (OPC) cultures were prepared from neonatal mouse cortex. The protective efficacies of the KRG components were examined against inhibitors of mitochondrial respiratory chain activity. For in vivo function of Rb1 on myelination, after 10 days of oral gavage into adult male mice, forebrains were collected. OPC proliferation were assessed by BrdU incorporation, and differentiation and myelination were examined by qPCR, western blot and immunocytochemistry. Results: The non-saponin promoted OPC proliferation, while the saponin promoted differentiation. Both processes were mediated by AKT and extracellular regulated kinase (ERK) signaling. KRG extract, the saponin and non-saponin protected OPCs against oxidative stress, and both KRG extract and the saponin significantly increased the expression of the antioxidant enzyme. Among 11 major ginsenosides tested, Rb1 significantly increased OL membrane size in vitro. Moreover, Rb1 significantly increased myelin formation in adult mouse brain. Conclusion: All KRG components prevented OPC deaths under oxidative stress. While non-saponin promoted proliferation, saponin fraction increased differentiation and OL membrane size. Furthermore, among all the tested ginsenosides, Rb1 showed the biggest increase in the membrane size and significantly enhanced myelination in vivo. These results imply therapeutic potentials of KRG and Rb1 for myelin-related disorders.

• Journal of Korean Medicine Rehabilitation
• /
• v.33 no.4
• /
• pp.215-223
• /
• 2023

The purpose of this study is to report the effects of Korean medicine treatment on the gait disorder. Patient with myelin oligodendrocyte glycoprotein-associated disorder. We treated the patient using Korean medicine treatment including Motion-Style-Acupuncture-Treatment, pharmacopuncture, acupuncture, and herbal medicine during 30 days. Numerical rating scale (NRS), EuroQol five dimension (EQ-5D) index, Oswestry Disability Index (ODI), Modified Barthel Index (MBI), and the changes of symptoms were measured for assessment. After 30 days inpatient treatment, NRS decreased from 4 to 2, EQ-5D index, ODI, MBI, and the symptoms of the patient also were improved. In conclusion, this case shows Korean medicine treatment might be an effective treatment for gait disorder Patient with MOG-associated disorder.

• Applied Microscopy
• /
• v.18 no.2
• /
• pp.187-204
• /
• 1988

The present experiment was performed to investigate the acute and subacute effect of lead acetate on ultrastructural and biochemical changes in mouse diencephalon. In acute case, mouse were peritoneally injected with lead acetate at a dose of 0.26 mmole/kg body weight, and after treatment, mouse were sacrificed at time intervals of 12, 24, 48, and 96 hours. In subacute case, mouse were injected at doses of 0.07 mmoie/kg B. W. and 0.13 mmole/kg B.W. once at two days, and after treatment, mouse wee sacrificed at 1 week, 2 weeks, and 3 weeks. It was observed that after acute treatment, changes composed of increased monoamine oxidase activity, $Na^{+}-K^{+}$ ATPase activity, decreased $Mg^{2+}$-APTase activity, wrinkled myelin, swollen Golgi apparatus and more dense synaptic vesicle in nerve terminal. After subacute treatment, decreased monoamine oxidase activity, increased $Mg^{2+}$-ATPase, $Na^{+}-K^{+}$ ATPase, lose of myelin, uneven mitochondrial distribution, synaptic vesicular density and edema, but at a higher dose the effect was more severe. Therefore, lead acetate caused abnormal change of diencephalon, and at a subacute, it appears metal accumulative toxicity.

• The Korean Journal of Zoology
• /
• v.33 no.4
• /
• pp.454-460
• /
• 1990

The effed of acrylamide on the nervous system has heen morphologically studied using light and electron microscopes. The light micrographs on central and pedpheral nervous tissues of mouse treated with acrylamide monomer showed total vacuolation of spinal cord, cell degradation containing neuron and neuroglia, and distal nerve fiber degeneration. The electron micrographs showed ultrastrudural changes. Abnormal mitochondria in neuron, splitting of myelin sheath in lumbar ventral root nerve, partial disintergration of myelin sheath and axoplasmic degeneration in sciatic nerve, and overafl polyneuropathies in nervous system were observed. These results suggest that acrylarnide intoxicated mouse shows distal behavioral neuropathy as an earlist clinical sign, but the initial effect of acrylamide on the nervous system seems to appear at nearly the same time in both central and peripheral nervous systems.

• Journal of Genetic Medicine
• /
• v.10 no.2
• /
• pp.88-93
• /
• 2013

Alexander disease (ALXD) is a rare demyelinating disease of the white matter of the brain that is caused by a mutation in the glial fibrillary acidic protein (GFAP) gene. The overexpression of GFAP in astrocytes induces a failure in the developmental growth of the myelin sheath. The neurodegenerative destruction of the myelin sheath of the white matter is accompanied by an accumulation of abnormal deposits of Rosenthal fibers in astrocytes, which is the hallmark of ALXD. The disease can be divided into four groups based on the onset age of the patients: neonatal, infantile, juvenile, or adult. Early-onset disease is more severe, progresses rapidly, and results in a shorter life span than late-onset cases. Magnetic resonance imaging and genetic tests are mostly used for diagnostic purposes. Pathological tests of brain tissue for Rosenthal fibers are definitive diagnostic methods. Therapeutic strategies are being investigated. Ceftriaxone, which is an enhancer of glial glutamate transporter (GLT-1) expression, is currently in clinical trials for the treatment of patients with ALXD. To date, there are no clinically available treatments. The cause, pathology, pathophysiology, inheritance, clinical features, diagnosis, and treatment of ALXD will be reviewed comprehensively.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1993.04a
• /
• pp.135-135
• /
• 1993

신호전달과정에 중요한 역할을 하고 있는 다기능 serinei/threonine 단백질인산화효소인 protein kinase C(PKC)의 연구를 위해 이 효소의 정제를 뇌에서 착수하였다 PKC의 활성측정을 myelin basic protein을 기질로 하여 20 mM Tris 완충용액 PH 7.5, 0.15 mM [${\gamma}$-$^{32}$P]ATP(3 $\times$ $10^{5}$ cpm), 0.1 mM $Ca^{2＋}$, 10$\mu\textrm{g}$ phosphatidylserine과 2$\mu\textrm{g}$ diolein을 넣어 반응시켰다. 반응은 TCA로 정지시킨 후 방사성 단백질을 Millipore filter paper로 걸러 섬광 계수기로 읽었다. Cytosol PKC의 정제과정은 첫 단계에서 DEAE-cellulose를 사용하였으며, phenyl sepharose CL-4B와 protamine agarose를 연속적으로 이용하여 800배의 정제에 성공했다. SDS-PACE 상에서 80 kD로 나타났으며 순도는 95 % 이상이였다. 이를 이용 PKC의 각종 기질 연구에 착수하기 시작했으며, 이중 MBP의 인산화연구를 통한 myelin의 안정성과 MBP와의 구조 관계가 일부 수행되고 있다 연차적으로 PKC와 이와 관련된 단백질의 특성을 살피기 위해 뇌의 PKC 기질 중 cold stress를 통해 환경에 민감한 것을 찾고 있으며, 현재 autoradiography를 이용해 80 kD, 54 kD, 49 kD와 35 kD의 단백질이 연구대상이 되고있다. 그 중 49 kD는 B-50(또는 GAP43, neuromodulin이라고도 함)일 가능성이 높아 이 단백질 조절과 PKC 활성화 사이의 관계 정립이 흥미로운 과제로 대두되고 있다.다.

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2002.05a
• /
• pp.14-23
• /
• 2002

Development of oligodendrocytes and the generation of myelin internodes within the spinal cord depends on regional signals derived from the notochord and axonally derived signals. Neuregulin (NRG)-1, localized in the floor plate as well as in motor and sensory neurons, is necessary for normal oligodendrocyte development. Oligodendrocytes respond to NRGs by activating members of the erbB receptor tyrosine kinase family. Here, we show that erbB2 is not necessary for the early stages of oligodendrocyte precursor development, but is essential for proligodendroblasts to differentiate into galactosylcerebroside-positive (GalC+) oligodendrocytes. In the presence of erbB2, oligodendrocyte development is normal. In the absence of erbB2 (erbB2-/-), however, oligodendrocyte development is halted at the proligodendroblast stage with a >10-fold reduction in the number of GalC+ oligodendrocytes. ErbB2 appears to function in the transition of proligodendroblast to oligodendrocyte by transducing a terminal differentiation signal, since there is no evidence of increased oligodendrocyte death in the absence of erbB2. Furthermore, known survival signals for oligodendrocytes increase oligodendrocyte numbers in the presence of erbB2, but fail to do so in the absence of erbB2. Of the erbB2-/- oligodendrocytes that do differentiate, all fail to ensheath neurites. These data suggest that erbB2 is required for the terminal differentiation of oligodendrocytes and for development of myelin.

• Journal of Veterinary Clinics
• /
• v.19 no.3
• /
• pp.316-321
• /
• 2002

The purpose of this study was to examine the effect of Ga-As(Gallium-Arsenide, wave length; 904 nm) infrared laser irradiation on healing of the experimentally crush injured rat sciatic nerves. The bilateral sciatic nerves of 43 adult male Sprague-Dawley rats were compressed surgically with a straight hemostat (1 mm width). The right legs of all the rats were irradiated using a 27 mW Ga-As infrared laser (laser irradiated group). The radiation procedure was administered for 3 minutes every day for 1, 3, 5, and 7 weeks in each group. Left legs were not irradiated and served as the control group. The numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs were measured and analyzed with mage analysis system in order to make a morphological analysis of the effect of the Ga-As infrared laser on injured nerves. Total number of myelinated axons was increased with time interval, especially in the 1, 3. and 5 week of irradiated group. Conversely, the number of degenerated myelin was decreased with time interval, especially in the irradiated group. The effects in the irradiated group were more pronounced than those of the control group. In conclusion, the Ga-As infrared laser irradiation is a useful adjuvant therapy to the regeneration of the peripheral nerve injury.