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Effect of Carbon Monoxide on the Nogo-A of Oligodendrocytes Cultured in Vitro

Author: CheJuHua
Tutor: WangSuPing
School: Dalian Medical University
Course: Neurology
Keywords: Carbon monoxide Oligodendrocytes Nogo-A Heme oxygenase
CLC: R747.9
Type: Master's thesis
Year: 2008
Downloads: 48
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Abstract


Background and Objective: Acute carbon monoxide poisoning (acute carbon monoxide poisoning, ACMP) is more common career and life of poisoning, can cause central nervous system (centeral neverous system, CNS) injury. After the disappearance of some patients with acute symptoms of poisoning appear showed normal or near normal after a few days or a few weeks leave more of neuropsychiatric symptoms of dementia mainly known as acute carbon monoxide poisoning with delayed encephalopathy (delayed encephalopathy after acute carbon monoxide white matter demyelination poisoning DEACMP), DEACMP brain imaging in patients with significant [1-4]. Leave more of the presence to DEACMP early diagnosis difficult, difficult to effectively combat heavy burden to society family. its receptor (Nogo-receptor, NgR) are widely distributed in a variety of neurons, also present in glial cell gap seam junction prompted NgR connection between glial cells to regulate through the slot, but oligodendrocytes The cells themselves no NgR distribution [6]. These make the Nogo-A and NgR become a key factor in limiting nerve regeneration and axonal damage repair [7]. Nogo-A is involved in the ACMP brain damage the pathogenesis of DEACMP has not been reported. White matter demyelination prominent view of the Nogo-A protein NgR distribution characteristics, and DEACMP patients with brain imaging, we speculated that the Nogo-A protein, and NgR ACMP brain damage, especially closely related DEACMP. The morpholine -9 (Zinc Porphyrin IX, ZnPPIX) inhibits CO production, has been used to study endogenous CO neuroendocrine regulation [8]. As the only enzyme system of in vivo synthesis of endogenous CO, HO-CO system is increasingly concerned about the Nogo-A and NgR has also been reported. The experiment, to exclude the effects of hypoxia, we deal directly with exogenous CO cultured oligodendrocytes in vitro inhibition of HO activity with ZnPPIX observed oligodendrocyte Nogo-A expression at the mRNA and protein levels, Nogo-A may exist in the ACMP brain damage and DEACMP of pathophysiological mechanisms, in order to explore a new experimental basis for the study of the ACMP brain damage and DEACMP the pathogenesis and treatment. Methods: (1) from newborn two days of the optic nerve of SD rats using tissue culture method limited cultured in medium with DMEM/F12 chemical, purified oligodendrocytes. Immunocytochemistry detected oligodendrocyte myelin basic protein (Myelin basic protein, MBP) expression, identified oligodendrocytes, and calculated the positive rate. (2) to exclude the influence of hypoxia, 1% CO treatment oligodendrocytes glial cells, using RT-PCR and Immunohistochemical observation of 6h, 24h, 48h oligodendrocyte the Nogo-AmRNA and the protein expression. (3) to take express Nogo-AmRNA, the highest point in time, pre-added ZNPP-IX inhibition of HO activity, 1% CO treatment oligodendrocytes, glial cells, detection the Nogo-AmRNA and its protein. Results: 1, organizations block 24h start adherent, 48h-72h visible edge of the nerve tissue to swim out to a small number of cells, the main round. Basic 9-10d cells from the tissue blocks freed tiles on the bottom of the dishes. 11d about basic cell bodies were round or polygonal, diameter approximately 6-10μm larger the nucleus, cytoplasmic processes rich, interwoven into a network. Cells Immunocytochemical MBP protein positive, more than 95% positive cells. 2, RT-PCR detected the expression of Nogo-AmRNA; (1) control group: 6h, for 24h, 48h have Nogo-A mRNA expression were: 0.733 ± 0.034,0.705 ± 0.027,0.717 ± 0.04, and not reflected in its expression with the Time change significantly; CO Group: 6h, 24h, 48h Nogo-AmRNA expression were: 1.042 ± 0.015,1.304 ± 0.008,0.937 ± 0.005, and the control group compared with a significant difference (P lt; 0.05). (2) ZNPP-IX group with pure CO treatment group (COZN) compared the Nogo-AmRNA increase in value: 1.454 ± 0.041,1.278 ± 0.032, (P lt; 0.01), a statistically significant difference. Immunocytochemistry detection Nogo-A protein expression: Nogo-A expression in the membrane and cytoplasm of oligodendrocytes is tan. Immunocytochemistry image analysis results show that: (1) Control group 6h, 24h, 48h have Nogo-A protein expression, no expression change significantly over time, the cumulative optical density value: 2836.74 ± 94.30; 2761.16 ± 75.80 ; 2780.16 ± 95.46; CO group 6h, 24h, 48h accumulated optical density value: 4087.20 ± 79.28; 7240.40 ± 63.25; 3449.90 ± 93.46; CO group at all time points accumulated optical density value of a statistically significant difference compared with the Control group (P lt; 0.05) (3) ZNPP-IX group: ZNPP-IX intervention after Nogo-A protein expression was increased compared with pure CO treatment group (COZN), a statistically significant difference (P lt; 0.05), the total optical density value respectively. is: 7159.41 ± 97.32; 9880.76 ± 105.81. Conclusion: (1) exclude the impact of hypoxia induced by exogenous CO vitro cultured oligodendrocyte Nogo-A mRNA and protein expression. (2) exclude the impact of hypoxia induced by exogenous CO vitro cultured oligodendrocyte Nogo-A mRNA expression increased, HO-CO system Nogo-A mRNA and protein expression was inhibited.

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