engleski

Are heterotopic motoneurons in spinal muscular atrophy actually adult stem cells?

The origin and role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still a matter of debate. In our recent paper (Simic et al., Acta Neuropathol. 2008) we have shown that, unlike controls, SMA patients with confirmed homozygous deletion of exon 7 in the SMN1 gene display a significant number of HMN at all levels of spinal cord. A quantitative analysis showed a negative correlation between the number of HMN and age of SMA subjects (a reflection of the clinical severity). HMN are located in the ventral white matter and anterior roots, have no axon or dendrites and look hyperchromatic in Nissl-stained sections. Since most of them show immunonegativity for markers of mature, differentiated neurons (e.g. NeuN and MAP2 proteins), this raises the possibility that some of them may represent resident adult stem cells. We hope that the analysis of nestin (which is expressed predominantly in neural stem cells and not in mature cells of the central nervous system) and developmental markers of motor neurons (such as islet, lim and HB9) in postmortem spinal cord tissue of genetically confirmed SMA patients will be sufficient to give an adequate answer to this hypothesis.

migration; motoneurons; neural stem cells; SMN1 gene; SMN protein; spinal muscular atrophy

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