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Stimulating Corticospinal Tract Axon Regeneration

EVENT: 
Weekly Seminar
Who Should Attend: 
Researchers

Speakers

Host
Jian's Photo
Lab Director
Burke Neurological Institute
Associate Professor of Neuroscience
Weill Cornell Medicine
Co-Director
Burke Neurological Institute

Abstract

In our laboratory we study how limited numbers of genes orchestrate the axon growth program to build the neuronal network in the mammalian fetus, and then attempt to activate these same mechanisms to enable axon regeneration in the injured adult nervous system. Failure of axonal rewiring after spinal cord injury is the reason that its victims typically remain paralyzed for life. We have identified the RAF - MEK kinase pathway as a key signaling mediator in the program of axon growth. Activation of this pathway in genetically modified mice triggers the expression of multiple regeneration-associated genes and promotes robust regenerative corticospinal tract axon growth, both elongation and collateral sprouting. Newly extending corticospinal axons form synaptic connections with spinal interneurons, and we documented improved recovery of voluntary locomotion in murine models of spinal cord injury. Aiming to translate the finding into the clinic, we found that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS), a non-invasive and clinically applicable technique, activated the kinases MEK1/2 in motor cortex. Post-injury HF-rTMS treatment triggered substantial CST axon regeneration and sprouting as well as sustained recovery of fine motor performance in wild type mice with spinal cord injuries. Moreover, its effects on regeneration and motor behaviors were fully abolished by conditional ablation of MEK1/2 in corticospinal neurons. Collectively, these data demonstrate a central role of neuron-intrinsic RAF MEK signaling for the rebooting of intrinsic axon growth programs in adult CSNs. We are now teaming up with clinicians to examine the feasibility and efficacy of HF-rTMS as a treatment option for spinal cord injury patients.

Dr. Zhong's Figure

Fig. High Frequency transcranial magnetic stimulation facilitates CST axon
regeneration in the spinal cord after injury (Manuscript submitted).

Publications

Boato F, Guan X, Nicola F, Zhu Y, Voutounou M, Freschlin F, Matho K, Sergey N. Makarov SN, Wu Z, Son Y-J, Z. Huang J, Nummenmaa A, Edwards DJ, Zhong J.
HF-rTMS instruments MAPK kinase signaling for axon growth and enhances recovery of voluntary motor control after CST injury
Submitted.
Ankur Garg, Abdul Hannan, Qian Wang, Neoklis Makrides, Jian Zhong, Hongge Li, Sungtae Yoon, Yingyu Mao, Xin Zhang
Etv Transcription Factors Functionally Diverge From Their Upstream FGF Signaling in Lens Development
Elife . 2020 Feb 11;9:e51915. doi: 10.7554/eLife.51915.
Kevin J O'Donovan, Kaijie Ma, Hengchang Guo, Chen Wang, Fang Sun, Seung Baek Han, Hyukmin Kim, Jamie K Wong, Jean Charron, Hongyan Zou, Young-Jin Son, Zhigang He, Jian Zhong
B-RAF Kinase Drives Developmental Axon Growth and Promotes Axon Regeneration in the Injured Mature CNS
J Exp Med . 2014 May 5;211(5):801-14. doi: 10.1084/jem.20131780. Epub 2014 Apr 14.

When

Tuesday, July 7, 2020 - 12:30pm

Where

Conference Room: 
LIVE WEBINAR

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