Lost neuronal function can be restored after injury in a roundworm model
07 Nov 2017
By Dr Anindya Ghosh-Roy, Intermediate Fellow
National Brain Research Centre (NBRC), Manesar
Damage to our nerve cells or neurons, due to an accident or physical stress can severely affect many aspects of normal life, for example our ability to walk, smell and see. It is observed that in adulthood the long nerve processes of injured neurons, known as axons, face a great deal of challenges in surviving and finding their way to reach the right partner neuron. Therefore, injured neurons are unable to transmit nerve signals properly and our ability to recover from this functional loss is mostly partial and this ability decays with age.
In experimental models of nerve regeneration, in some neurons, it is noticed that after injury, axonal fragments can rejoin by self-fusion. This phenomenon is termed as axonal fusion. A group of students from our laboratory at the National Brain Research Centre, Manesar, found that this process of axonal fusion restores lost function after injury. In our laboratory, we are using Caenorhabditis elegans (C. elegans), a non-parasitic roundworm, to study neuronal response to injury. C. elegans sensory neurons are responsible for touch sensation. We found that fusion between proximal and distal fragments of injured neuron promotes recovery of function. This study also identified a regulatory mechanism controlling this process.
To study the behavioral consequence of neuronal breakage, our collaborators had to first find a way to cut axonal processes located deep inside the worm's body. They used two femotosecond lasers simultaneously, one to locate and the other to cut the neurons of their interest.
It is important to study neuronal regeneration at functional level because the significance of regrowth lies in its behavioral recovery. Although it is not clear whether axonal fusion would help recover the lost function after large injury, which breaks many axons in our nerve bundles, this phenomenon might come into action after spontaneous breakage of axonal process during day-to-day stress induced injury. Nevertheless, it stimulates many research questions to study molecular mechanism of axonal fusion using various model organisms.
The research team also included researchers from the Tata Institute of Fundamental Research (TIFR) , Mumbai and Bruker India Scientific Pvt Limited.
let-7 miRNA controls CED-7 homotypic adhesion and EFF-1–mediated axonal self-fusion to restore touch sensation following injury. Atrayee Basu, Shirshendu Dey, Dharmendra Puri, Nilanjana Das Saha, Vidur Sabharwal, Pankajam Thyagarajan, Prerna Srivastava, Sandhya Padmanabhan Koushika, and Anindya Ghosh-Roy. PNAS. November 2017
Banner image credit: Harjot Kaur & Anindya Ghosh Roy
Image description: The nematode C. elegans with GFP labeled touch neurons. Axons in tail region were severed with laser and imaged one day later. We show that when the injured axonal fragments recognize each other and rejoin (worm shown above) the lost function is restored. However, when the proximal stump fails to join the distal fragment (worm shown below) the function remains impaired.