Directing neuronal regeneration
Axons are long slender projections of neurons and are responsible for transmitting information. Axonal growth capacity normally ends during foetal development and they do not regenerate after injury. External interventions have limited success as regenerating axons are unable to penetrate the stiff glial scar tissue formed after SCI. Scientists of the MAGFORCE4AXONGROWTH project worked on elucidating relevant signalling pathways involved in modulating growth cone migration and axon regeneration. They synthesised magnetic nanoparticles to apply the requisite mechanical tension for the so-called axon-pulling experiments. To begin with, researchers developed a microfluidic neuron culture device for primary cortical neurons obtained from embryonic mice. Axon growth cones were targeted through coating with antibodies specific for neuronal cell adhesion molecule (NCAM). Researchers then developed and employed a magnetic tweezer-based microfluidic system for application of controlled force that mimics forces generated by neuronal growth cones. Applying chemical stimuli, the researchers assessed their effect on axon outgrowth and identified potential targets for therapy. The role of Semaphorin 3A and Netrin 1 was studied to understand the function of associated signal transduction pathways. Results revealed that targeting the Rho kinase (ROCK) and Calpain signalling pathways would prove effective in combination with axon pulling experiments. Inhibition of the ROCK pathway along with application of magnetic forces redirected NCAM-mediated axonal growth towards the glial scar environment. Project activities have opened up novel therapeutic avenues for treating SCI and neurodegenerative disorders. Their successful translation into clinical practice would improve the quality of life of such patients and significantly reduce the associated socioeconomic burdens.
Keywords
Spinal cord injury, neuronal regeneration, growth cone, axon, glial scar tissue, signaling pathway, nanoparticles, axon pulling, magnetic tweezer, ROCK, Calpain
