論文紹介著者

Liang Zhang（博士課程 2年）
GCOE　RA
Department of rehabilitation medicine

第一著者名・掲載雑誌・号・掲載年月

Yasir A. Syed／J Neurosci. 2011 Mar 9;31(10):3719-28.

文献の英文表記：著者名・論文の表題・雑誌名・巻・号・ページ・発行年（西暦）

Syed YA, Hand E, Mobius W, Zhao C, Hofer M, Nave KA, Kotter MR. Inhibition of CNS remyelination by the presence of semaphorin 3A. J Neurosci. 2011 Mar 9;31(10):3719-28.

論文解説

Introduction

Multiple sclerosis (abbreviated MS) is an inflammatory disease in which the fatty myelin sheaths^*1 around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. A person with MS can suffer almost any neurological symptom or sign, including changes in sensation, muscle weakness, clonus, muscle spasms, or difficulty in moving; difficulties with coordination and balance; problems in speech or swallowing, visual problems, fatigue, acute or chronic pain, and bladder and bowel difficulties.

Oligodendrocyto precursor cells are the major remyelinating players in the adult CNS. Recently, failure of oligodendrocyte precursor cell (OPC)^*2 differentiation has been recognized as a reason of demyelination diseases such as MS, although the mechanism of which contribute to this failure has not been elucidated clearly. Semaphorin3A, which is a repulsive guidance cue for neuronal and glial cells in CNS, expressed in active MS lesions. However, the roles of Sema3A expression in MS remain unclear.

Summary

To identify whether Sema3A inhibits CNS remyelination and play an important role in the differentiation block occurring in MS lesions, authors administrated Sema3A into demyelinating lesions in rat CNS. This work showed that only the presence of Sema3A resulted in a reduction of differentiatin O4-positive OPCs, which means sema3A selectively inhibits the differentiation of OPCs into oligodendrocytes. This inhibition is dose-dependent and reversible. Sema3A does not alter the macrophage^*4 response and the presence of OPCs in demyelinated lesions. It only arrests OPCs at a premyelinating state.

The inhibition of OPC differentiation by Sema3A is reversible. Cells inhibited as long as Sema3A was present in the medium(72h).However, this outcome was reversed following replacement with non-Sema3A containing medium

Conclusion

Extrinsic environment factors, such as Semaphorin3A, are implied play an important role in the differentiation block occurring in MS lesions. It can be regards as regulators and inhibitors in OPC migration and differentiation. This study opened new avenues to understand remyelination failure and promote repair in MS. Thus it provided a new target for the treatment of clinical demyelinating cases.

用語解説

• *1　Myelin sheath is a dielectric material that forms a layer around the axon of a neuron. It is essential for the proper functioning of the nervous system.
• *2　Oligodendrocyte precursor cell (OPC) in nervous tissue cells precede oligodendrocytes, and may also be able to generate neurons and astrocytes. The principal function of oligodendrocytes is to provide support to axons and to produce the Myelin sheath in CNS.
• *3　Semaphorin3A is one of the semaphorins which are large family of guidance molecules. It is produced by meningeal fibroblasts of the gilal scar and is the best studied semaphorins in spinal cord injury. Semaphorins not only serve as neurite repulsion and attraction, but also play important roles in such as immune modulation, organogenesis, angiogenesis, neuronal apoptosis and neoplastic transformation.
• *4　Macrophages play an important role in the process of remyelination.