News & Impact

You are here

Genetic or transcranial magnetic stimulation of B-RAF–MEK signaling promotes CST axon sprouting and functional regeneration

Francesco Boato, Xiaofei Guan, Yanjie Zhu, Youngjae Ryu, Mariel Voutounou, Christopher Rynne, Chase R. Freschlin, Paul Zumbo, Doron Betel, Katie Matho, Sergey N. Makarov, Zhuhao Wu, Young-Jin Son, Aapo Nummenmaa, Josh Z. Huang, Dylan J. Edwards, Jian Zhong
Year Published: 
BioRxiv. 2022 June 3. doi:10.1101/2022.06.01.494346
Full-Text on BioRxiv


Facilitating axon regeneration in the injured central nervous system remains a challenging task. RAF–MEK signaling plays an important role in axon elongation during nervous system development. Here we show that activation of B-RAF in mature corticospinal neurons elicited the expression of a discrete set of transcription factors previously implicated in the regeneration of zebrafish optic nerve axons. Genetic activation of B-RAF–MEK signaling promoted robust regeneration and sprouting of corticospinal tract axons after injury. Newly sprouting axon collaterals formed synaptic connections with spinal interneurons, correlating with the recovery of skilled motor function. Seeking a non-invasive way to stimulate axon regeneration, we found that suprathreshold high-frequency repetitive transcranial magnetic stimulation activates the B-RAF canonical effectors MEK1/2 and requires MEK1/2 activity to promote corticospinal axon regeneration and sprouting after injury. These data demonstrate a central role of neuron-intrinsic RAF–MEK signaling in enhancing the growth capacity of mature corticospinal neurons and propose HF-rTMS as a potential therapy for spinal cord injury.

Conditions & Recovery

Spinal Cord Injury icon
Around the world, between 300,000 and 500,000 people are living with a SCI.
Pain and Sensory Recovery Icon
Pain free, touch and smell like before.

Research Methods