overview: High-frequency repetitive transcranial magnetic stimulation (rTMS) activates MAP2K signaling and promotes axonal regeneration and functional recovery after spinal cord injury.
A new study by the Burke Neurological Institute (BNI), Weill Cornell Medicine, shows that activation of MAP2K signaling by genetic engineering or by repetitive noninvasive transcranial magnetic stimulation (rTMS) reduces corticospinal tract (CST) axons after spinal cord injury. It was found to promote germination and functional regeneration. (SCI) in mice.
rTMS is a non-invasive technique that induces electric fields in brain tissue via electromagnetic induction. Although there is increasing evidence to suggest that application of rTMS to the motor cortex may be beneficial for functional recovery in patients with SCI, the molecular and cellular mechanisms underlying the beneficial effects of rTMS remain unclear.
New research published in science translation medicine have shown that high-frequency rTMS (HF-rTMS) activates MAP2K signaling and promotes axonal regeneration and functional recovery, suggesting that rTMS may be a valuable therapeutic option for patients with SCI. increase.
Promoting axonal regeneration in the injured central nervous system (CNS) remains a challenging task. The inability of mature CNS neurons to activate cell-intrinsic growth mechanisms and regenerate damaged axons significantly hinders the development of effective new therapies after traumatic brain or spinal cord injury.
The RAF-mitogen-activated protein kinase kinase (MAP2K, also known as MEK) signaling cascade mediates long-distance axonal outgrowth in developing PNS and CNS neurons. Based on previous findings, BNI investigators believe that RAF signaling regulates an intrinsic axonal growth program, activation of which enables regrowth of adult mammalian CNS axons after his SCI. I hypothesized that there is.
They show that the conditional expression of constitutively kinase-activated BRAF in mature corticospinal neurons (CSNs) leads to the expression of a series of transcription factors previously implicated in axonal regeneration in zebrafish retinal ganglion cells. was found to induce
Moreover, conditional BRAF activation in the CSN enabled CST axonal sprouting and regeneration in various experimental models of SCI in mice. According to her BNI postdoctoral researcher, Xiaofei Guan, M.D., Ph.D., who conducted the experiment, her newly sprouted CST axons synapse with local spinal cord circuits, further enhancing motor function recovery. brought improvement.
Although rTMS has emerged as a promising strategy to enhance recovery in patients with spinal cord or brain injuries, the plasticity mechanisms underlying these approaches and their full therapeutic potential remain unclear.
A BNI research team found that a course of daily high-frequency rTMS sessions activates MAP2K signaling and regulates the expression of a set of regeneration-associated transcription factors in the same way as genetic BRAF activation. Endogenous MAP2K activity was required for enhanced her CST sprouting, regeneration, and functional recovery in SCI model mice treated with HF-rTMS.
The researchers believe that these results collectively point to a central role for MAP2K signaling in enhancing the growth potential of mature CSNs, suggesting that HF-rTMS may regulate MAP2K signaling by It has been suggested that it may treat spinal cord injuries.
The BNI team has initiated a clinical trial testing the HF-rTMS protocol in healthy subjects and patients with SCI. If successful, HF-rTMS could be a noninvasive way to promote axonal regeneration alone or in combination with other additional interventions for SCI or other individuals who may benefit from CNS circuit repair. could emerge as a more targeted, lower-risk treatment option.
About this spinal cord injury research news
author: press office
contact: Press Office – BNI
image: image is public domain
Original research: open access.
Francesco Boato et al Science Translational Medicine
Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes sprouting and functional regeneration of corticospinal axons
Promoting axonal regeneration in the injured central nervous system remains a challenging task. RAF-MAP2K signaling plays an important role in axonal outgrowth during nervous system development.
Here, conditional expression of constitutively kinase-activated BRAF in mature corticospinal neurons induced expression of a set of transcription factors previously implicated in zebrafish retinal ganglion cell axon regeneration. , we show that it promoted regeneration and sprouting of corticospinal tract (CST) axons. After spinal cord injury in mice.
Newly sprouted axon-lateral lobes formed synaptic connections with spinal interneurons and improved recovery of motor function.
Noninvasive threshold ultrahigh-frequency repetitive transcranial magnetic stimulation (HF-rTMS) activates the BRAF canonical downstream effectors MAP2K1/2 and expresses a set of regeneration-associated transcription factors consistent with the pattern induced by BRAF activation. adjusted by pattern. HF-rTMS enabled regeneration and sprouting of her CST axons, which were abolished in MAP2K1/2 conditional null mice.
Collectively, these data demonstrate a central role for MAP2K signaling in enhancing the growth potential of mature corticospinal neurons and the potential for HF-rTMS to treat spinal cord injury by modulating MAP2K signaling. suggests that there is