Researchers at the Hong Kong University of Science and Technology (HKUST) have found a way to stimulate the growth of axons, which may spell the dawn of a new beginning on chronic SCI treatments.
Chronic spinal cord injury (SCI) is a formidable hurdle that prevents a large number of injured axons from crossing the lesion, particularly the corticospinal tract (CST). Patients inflicted with SCI would often suffer a loss of mobility, paralysis, and interferes with activities of daily life dramatically. While physical therapy and rehabilitation would help the patients to cope with the aftermath, axonal regrowth potential of injured neurons was thought to be intractable.
This sagittal section shows the regeneration of mouse corticospinal tract axons (red) 7 months after Pten deletion was initiated in motor cortex. Pten deletion was initiated 1 year after spinal cord injury in this mouse. Green labels glial fibrillary acidic protein.
Credit: Division of Life Science, HKUST
No outside stimulants are needed; the growth driver lies within the neurons themselves.
Inside our DNA, in particular.
In the July 1st issue of The Journal of Neuroscience, HKUST researchers report that the deletion of the PTEN gene would enhance compensatory sprouting of uninjured CST axons. Furthermore, the deletion up-regulated the activity of another gene, the mammalian target of rapamycin (mTOR), which promoted regeneration of CST axons. Axons transmit information to different neurons, muscles, and glands; as bundles they help make up nerves.
Led by Kai Liu, PhD, the study's senior author and assistant professor in life sciences at HKUST, the research team initiated PTEN deletion on mice after pyramidotomy. Similar treatment procedures were carried out on a 2nd group 4 months after severe spinal cord injuries, and a 3rd group after 12 months.
The team recorded a regenerative response of CST axons in all 3 samples--showing that PTEN deletion stimulates CST sprouting and regeneration, even though the injury was sustained a long time ago.
"As one of the long descending tracts controlling voluntary movement, the corticospinal tract (CST) plays an important role for functional recovery after spinal cord injury," says Professor Liu. "The regeneration of CST has been a major challenge in the field, especially after chronic injuries. Here we developed a strategy to modulate PTEN/mTOR signaling in adult corticospinal motor neurons in the post-injury paradigm."
"It not only promoted the sprouting of uninjured CST axons, but also enabled the regeneration of injured axons past the lesion in a mouse model of spinal cord injury, even when treatment was delayed up to 1 year after the original injury. The results considerably extend the window of opportunity for regenerating CST axons severed in spinal cord injuries.
Compared with acute injury, axons face more barriers to regenerate after chronic SCI. Previously, scientists have shown that Axon retraction may further increase the distance that axons need to travel; Extracellular matrices, which become well consolidated around the chronic lesion site, also increases inhibition. Neuronal aging may also add obstacles to regrowth. In light of all of these challenges, it is indeed surprising to find that CST axons can still regenerate after 1 year.
"It is interesting to find that chronically injured neurons retain the ability to reform tentative synaptic connections," says Liu. "PTEN inhibition can be targeted on particular neurons, which means that we can apply the procedure specifically on the region of interest as we continue our research."
This study was supported in part by the Hong Kong Research Grants Council Theme-Based Research Scheme (Grant T13-607/12R), the National Key Basic Research Program of China (Grant 2013CB530900), the Research Grants Council of Hong Kong Special Administrative Region (Grants AoE/M-09/12, HKUST5/CRF/12R, AoE/M-05/12, C4011-14R, 662011, 662012, 689913, and 16101414), and the Hong Kong Spinal Cord Injury Fund.
Anita Lam | EurekAlert!
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Materials Sciences
05.12.2016 | Power and Electrical Engineering