6 May 2022
A research team led by Aya Takeoka (NERF, empowered by imec, KU Leuven, and VIB) has uncovered that specific types of nerve cells in the spinal cord undergo a switch after injury. This switch turns off communication with motor neurons that stimulate muscles and, therefore movement. Importantly, research in mice suggests that reversing this switch can dramatically improve functional recovery, especially in combination with physical training. The findings offer important insights for rehabilitation strategies for paraplegic patients and are published today in Nature Neuroscience.
Every year, about 10,000 people in Europe get into an accident that injures their spinal cord, leaving many of them with permanent paralysis of (part of) their body. As there currently exists no treatment to regenerate interrupted nerve fibers and repair the damaged spinal cord, 200,000 individuals in the EU live with the consequences of a spinal cord injury.
Prof. Aya Takeoka studies how neuronal circuits regulate movements and potentially help motor recovery after traumatic injury in her lab at Neuro-Electronics Research Flanders (NERF), a Leuven research institute empowered by imec, KU Leuven, and VIB. “There is still a lot we don’t understand about the plasticity of nerve cells, and this knowledge could potentially help patients with spinal cord injury,” Takeoka says.
Switching plasticity on and off
Research has shown that severe spinal cord injury in adults leads to irreversible paralysis below the lesion, while the same lesion occurring just after birth does not impair locomotion. “How the spinal cord can accomplish this in some situations but not always is still a mystery, and one of the central questions for researchers in our field,” explains Takeoka.
Together with her team, she set out to determine how age at injury and activity after injury affect the spinal cord neural circuit’s ability to reorganize itself.
“We found that adult spinal cord injury prompts certain nerve cells in the spinal cord to switch off their normal mode of communication, essentially reversing the signal they pass on to motor neurons, the nerve cells that finally innervate and activate the muscle,” says Hannah Bertels, a PhD student in the Takeoka lab.
Instead of stimulating their target connections, the occurrence of a spinal cord lesion causes these neurons to inhibit their contacts. Importantly, this switch did not occur when the injury happened at a young age.
The researchers took it one step further and explored whether intervening in this process could immediately affect the recovery process. Bertels: “We found that if we prevent this switch in communication, the ability to walk after injury indeed improved significantly, especially in combination with locomotor training.”
The reverse was also true: forcing the switch-off of the same nerve cells after injury at a very young age—where it normally does not occur—abolished the remarkable ability of these animals to walk without direct nerve signals from the brain, demonstrating once again that leaving the switch ‘on’ is essential.
“Together, these data demonstrate that the dynamic switch of specific spinal cord nerve cells regulates locomotor recovery after spinal cord injury,” says Takeoka. “While the clinical significance of these biological and mechanistic findings has yet to be explored, our results stress the importance of targeting a defined subset of nerve cells, combined with physical therapy, in rehabilitative strategies after spinal cord injury.”
Neurotransmitter phenotype switching by spinal excitatory interneurons regulates locomotor recovery after spinal cord injury
Bertels et al. Nature Neuroscience 2022