• Molecules and Cells
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• 제40권6호
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• pp.426-433
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• 2017

Ephrin-A5 has been implicated in the regulation of brain morphogenesis and axon pathfinding. In this study, we used bacterial homologous recombination to express a LacZ reporter in various ephrin-A5 BAC clones to identify elements that regulate ephrin-A5 gene expression during mesencephalon development. We found that there is mesencephalon-specific enhancer activity localized to a specific +25.0 kb to +30.5 kb genomic region in the first intron of ephrin-A5. Further comparative genomic analysis indicated that two evolutionary conserved regions, ECR1 and ECR2, were present within this 5.5 kb region. Deletion of ECR1 from the enhancer resulted in disrupted mesencephalon-specific enhancer activity in transgenic embryos. We also found a consensus binding site for basic helix-loop-helix (bHLH) transcription factors (TFs) in a highly conserved region at the 3'-end of ECR1. We further demonstrated that specific deletion of the bHLH TF binding site abrogated the mesencephalon-specific enhancer activity in transgenic embryos. Finally, both electrophoretic mobility shift assay and luciferase-based transactivation assay revealed that the transcription factor Ascl1 bound the bHLH consensus binding site in the mesencephalon-specific ephrin-A5 enhancer in vitro. Together, these results suggest that the bHLH TF binding site in ECR1 is involved in the positive regulation of ephrin-A5 gene expression during the development of the mesencephalon.

• Molecules and Cells
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• 제38권11호
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• pp.1013-1021
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• 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 Korean Neurosurgical Society
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• 제56권6호
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• pp.475-481
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• 2014

Objective : To evaluate the anatomical feasibility of 3.5 mm screw into the cervical spine in the pediatric population and to establish useful guidelines for their placement. Methods : A total of 37 cervical spine computerized tomography scans (24 boys and 13 girls) were included in this study. All patients were younger than 10 years of age at the time of evaluation for the period of 2007-2011. Results : For the C1 screw placement, entry point height (EPH) was the most restrictive factor (47.3% patients were larger than 3.5 mm). All C2 lamina had a height larger than 3.5 mm and 68.8% (51/74) of C2 lamina had a width thicker than 3.5 mm. For C2 pedicle width, 55.4% (41/74) of cases were larger than 3.5 mm, while 58.1% (43/74) of pedicle heights were larger than 3.5 mm. For pedicle width of subaxial spine, 75.7% (C3), 73% (C4), 82.4% (C5), 89.2% (C6), and 98.1% (C7, 1/54) were greater than 3.5 mm. Mean lamina width of subaxial cervical spine was 3.1 (C3), 2.7 (C4), 2.9 (C5), 3.8 (C6), and 4.0 mm (C7), respectively. Only 34.6% (127/370) of subaxial (C3-7) lamina thickness were greater than 3.5 mm. Mean length of lateral mass for the lateral mass screw placement was 9.28 (C3), 9.08 (C4), 8.81 (C5), 8.98 (C6), and 10.38 mm (C7). Conclusion : C1 lateral mass fixation could be limited by the morphometrics of lateral mass height. C2 translamina approach is preferable to C2 pedicle screw fixation. In subaxial spines, pedicle screw placement was preferable to trans-lamina screw placement, except at C7.