Intracerebral Increase of CISD2 Expression Following Spinal Cord Injury in Mice-a Novel Role for Inflammatory Suppressor in the Central Nervous System
| Autor: | Li-Lin Jiang, 江理琳 |
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| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 CISD2 (CDGSH iron sulfur domain 2) is a novel gene. Recent researches have suggested that the loss of CISD2 expression would cause the structural damage of mitochondria. As soon as functional mitochondrial disorders, muscle and nerve cells to result in a recession, degeneration, and premature aging symptoms. We previously reported that with siRNA technology to remove (Knockdown) CISD2 gene, the neurons abundantly expressed iNOS (Inducible nitric oxide synthase). Next, we would like to know the role of CISD2 in brain after spinal cord injury, which is the major objective of this experiment in mice models of spinal cord hemisection to investigate the relation. In this experiment, we used five of eight-week-old ICR male mice in each group. Experimental groups included non-injured group and spinal cord injury group after 4, 12, 36 hours of SCI, and the injured groups treated by intravenous CISD2 antibody (100 μg/kg body weight) or Methylprednisolone (30 mg/kg body weight) within 30 min of SCI, which being sacrificed at 4, 12, 36 hours, respectively. We used RT-PCR, western blot and ELISA to detect TNF-α and CISD2 expression of brain at each time point. The results showed that the TNF-α mRNA expression in brain significantly increased at 4 hours of SCI, and then decreased after that. The CISD2 mRNA in brain significantly increased 12 and 36 hours, and protein expression at 36 hours. By immunofluorescence staining, we found that CISD2 is likely to expressed by neurons in brain after SCI. We detected the serum of CISD2 content and cerebrospinal fluid cytokine protein array, to figure out in which pathway to induce CISD2 expression in brain after SCI. We found that there is no CISD2 level in serum after SCI. In the protein array analysis, we found a lot of expression of pro-inflammatory cytokines in the cerebrospinal fluid after SIC. These data suggested that these inflammatory substances may flow to the brain via the cerebrospinal fluid to cause brain inflammation. Also, the data suggested that inflammation, being caused by SCI, might be able to cause inflammation in brain later. The inflammation in brain then abundantly induces CISD2 expression. It is possible to inhibit the TNF-α expression in a negative feedback effect. Therefore, we suggested that CISD2 has a novel role of anti- inflammation in CNS after SCI. Keywords: Spinal cord injury, CISD2, anti-inflammation, CNS. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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