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通过神经递质和胞磷胆碱调节骨髓实现脊髓再生:微观分子水平分析

Spinal cord regeneration by modulating bone marrow with neurotransmitters and Citicholine: Analysis at micromolecular level.

作者信息

Paulose Cheramadathukudiyil Skaria, John Ponnezhathu Sebastian, Chinthu Romeo, Akhilraj Puthenveetil Raju, Anju Thoppil Raveendran

机构信息

Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India.

Pushpagiri Institute of Medical Sciences and Research, Thiruvalla, Kerala, India.

出版信息

Biomed J. 2017 Apr;40(2):94-100. doi: 10.1016/j.bj.2016.11.006. Epub 2017 May 4.

Abstract

BACKGROUND

Spinal cord injury results in disruption of brain-spinal cord fibre connectivity, leading to progressive tissue damage at the site of injury and resultant paralysis of varying degrees. The current study investigated the role of autologous bone marrow modulated with neurotransmitters and neurotransmitter stimulating agent, Citicholine, in spinal cord of spinal cord injured rats.

METHODS

Radioreceptor assay using [3H] ligand was carried out to quantify muscarinic receptor. Gene expression studies were done using Real Time PCR analysis.

RESULTS

Scatchard analysis of muscarinic M1 receptor showed significantly decreased B (p < 0.001) and K (p < 0.01) compared to control and significant reversal (p < 0.001) in both the treatment groups (spinal cord injury treated with 5HT and GABA, and spinal cord injury treated with Citicholine). Muscarinic M1 receptor gene expression in spinal cord injured group showed significant down regulation (p < 0.001) compared to control, and both the treatment groups significantly reversed (p < 0.001) these changes to near control when compared to spinal cord injured group. The confocal microscopic study using specific antibody of muscarinic M1 confirmed the gene expression studies.

CONCLUSION

Thus our results suggest that the neurotransmitters combination along with bone marrow or Citicholine with bone marrow can reverse the muscarinic receptor alterations in the spinal cord of spinal cord injured rats, which is a promising step towards a better therapeutic intervention for spinal cord injury because of the positive role of cholinergic system in regulation of both locomotor activity and synaptic plasticity.

摘要

背景

脊髓损伤会导致脑脊髓纤维连接中断,进而导致损伤部位的组织逐渐受损,并引发不同程度的瘫痪。本研究调查了用神经递质和神经递质刺激剂胞磷胆碱调制的自体骨髓在脊髓损伤大鼠脊髓中的作用。

方法

使用[3H]配体进行放射受体分析以定量毒蕈碱受体。采用实时荧光定量PCR分析进行基因表达研究。

结果

与对照组相比,毒蕈碱M1受体的Scatchard分析显示B(p < 0.001)和K(p < 0.01)显著降低,并且在两个治疗组(用5-羟色胺和γ-氨基丁酸治疗的脊髓损伤组,以及用胞磷胆碱治疗的脊髓损伤组)中均有显著逆转(p < 0.001)。与对照组相比,脊髓损伤组中毒蕈碱M1受体基因表达显著下调(p < 0.001),与脊髓损伤组相比,两个治疗组均将这些变化显著逆转(p < 0.001)至接近对照水平。使用毒蕈碱M1特异性抗体的共聚焦显微镜研究证实了基因表达研究结果。

结论

因此,我们的结果表明,神经递质组合与骨髓或胞磷胆碱与骨髓一起可以逆转脊髓损伤大鼠脊髓中毒蕈碱受体的改变,由于胆碱能系统在调节运动活动和突触可塑性方面的积极作用,这是朝着更好地治疗脊髓损伤迈出的有希望的一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/827f/6138792/1a49eec22338/gr1.jpg

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