Researchers induce limb movement in paralysed mice


Activating an axon-regenerating pathway pays dividends. Biplab Das reports.


Mice able to exercise showed improved recovery from spinal cord injury.

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Researchers used a molecule-sized activator to fire up an axon-regenerating molecular pathway in paralysed mice, triggering the regeneration of the slender fibres that transmit electrical impulses to and from other neurons.

The finding, published in the journal Science Translational Medicine, was made by an international team, including researchers from the Imperial College London, UK, and the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, India, and could provide leads for improving conditions for patients with spinal cord injuries.

Axon regeneration fails in the brain and spinal cord after serious back or neck injury. But some studies have shown that using physical rehabilitation to boost the activity of neurons after injury can partially restore their regenerative potential.

However, little is known about how the process happens.

To uncover the mechanisms of axon regeneration, the researchers induced spinal cord injury in rodents and exposed them to different environmental conditions. Animals which were kept in large cages and allowed to use a running wheel recovered better than the those housed in a standard environment.

Lead author Thomas Hutson and colleagues found that at the heart of the regeneration process lay a protein with the unwieldy name of cyclic adenosine monophosphate-response element–binding protein–binding protein, abbreviated to Creb-binding protein, or Cbp.

Cbp modulates molecular pathways that are involved in gene expression, neuronal activity, axonal projection and cytoskeleton remodelling.

To understand its role in axon regeneration and its subsequent effects on animal behaviour, the researchers injected injured mice with a small molecule activator that boosts its activity.

They then exposed the treated animals to various tasks requiring the use of hind legs. Results were encouraging, with the animals demonstrating that they were responding to stimuli in the previously paralysed limbs.

The results of the research are encouraging, but rodent models do not fully replicate the pathology of spinal cord injury in humans, so any potential therapeutic targets have yet to be explored. Before this can happen, Hutson and colleagues say, further studies are needed to fully evaluate the toxicity profile of the molecule activator before it can be used in a clinical set-up.

  1. https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaw2064
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705788/
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