Chatty neurons; Responding microglia: TNTs allowing materials exchange
Work done in the lab of Prof. Chiara Zurzolo at Institut Pasteur, Paris, France
Ranabir Chakraborty received his bachelor’s degree in Zoology from Hansraj College, University of Delhi, and his master’s degree in biological sciences from Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India. After his master’s, he was a project student in Prof. Chandan Goswami’s lab in National Institute of Science Education and research, Bhubaneswar, India. There, he worked on several projects involving different thermosensitive ion channels and their functional roles in bone physiology, and microglial activity. He first reported the presence of cold-sensitive ion channel TRPM8 in microglia, besides the previously known presence of heat-sensitive TRPV4 channel. In Zurzolo lab, Ranabir is interested in dissecting out the (patho)physiological significance of TNTs in neuron-microglia interactions, from a broader perspective of neuroinflammation.
Author Interview
How would you explain your research outcomes to the non-scientific community?
Decades of research in the field of neuroscience was with a neuron-centric approach. Undoubtedly, that has led to a plethora of knowledge about the functionalities of the brain. However, the roles of equally important (if not more) non-neuronal cells (glia) in regulating homeostasis of the nervous system have started to be elucidated only in the last few decades. What the field of glia biology has now very well established is that different glial cells of the brain (astrocytes, microglia, oligodendrocytes, pericytes) can establish themselves within the framework of a functional neuronal network, and interact with neurons in a variety of ways.
One of the ways neuron-glia interactions are made possible is via long and thin intercellular connections called Tunneling Nanotubes (TNTs). We have discovered the presence of such functional connections between human neuronal and microglial cells, that allows the movement of Parkinson’s Disease causing -Synuclein aggregates, from neuronal to microglial cells, with a strict sense of directionality. On the other hand, microglia, the phagocytes of the brain, respond to neuronal stress by providing them with mitochondria.
“This work not only strengthens the idea that TNTs facilitate functional communication between neurons and microglia, but also puts these intercellular structures in the context of neurodegenerative pathologies, wherein TNTs might have a big role to play in the progression of diseases. “
How do these findings contribute to your research area?
Tunneling Nanotubes were first described in 2004, and TNTs are slowly, but steadily, getting recognized for their critical roles in mediating intercellular communication. The lab of Prof. Chiara Zurzolo has pioneered the field of TNTs and their roles in orchestrating the spread of aggregated proteins that cause neurodegenerative diseases in the last decade. Previous studies have shown that TNTs can form between similar cell types (such as neurons, astrocytes, microglia, and pericytes), as well as between two different cell types (such as neurons-astrocytes, and neuron-pericytes). However, our understanding of how neurons and microglia put in place TNTs between each other, and the consequence of such communication with respect to the kind of materials exchanged, was not known.
This work not only strengthens the idea that TNTs facilitate functional communication between neurons and microglia, but also puts these intercellular structures in the context of neurodegenerative pathologies, wherein TNTs might have a big role to play in the progression of diseases.
Additionally, the roles of microglia in neurodegenerative pathologies still remain debated, wherein depending on the stage of disease or other (yet unknown) microenvironmental contexts, the pathophysiological roles of microglia can vary within the spectrum of neuroprotective-neurotoxic. The fact that TNTs facilitate the transfer of aggregates from the aggregate-burdened neuronal cells to microglia, and of mitochondria to the distressed cells, suggest a potential protective role of microglia within the framework of our experimental design. This, however, will require further extensive studies in the future.
What was the exciting moment during your research?
Working on this project is an exciting venture. If I were to cherry-pick one, it would be the moment we saw bi-directional movement of aggregates and mitochondria through the same tube. These cells really know what they are talking about!
What do you hope to do next?
Currently, we are building on the project to understand the lengths of such communication between neurons and microglia, with respect to the environmental contexts that facilitate TNT-mediated communication.
Where do you seek scientific inspiration from?
My supervisor, Prof. Chiara Zurzolo, is undoubtedly a constant source of inspiration with her enthusiasm for this field. The field of academic research was introduced to me during my master’s program in JNCASR, and observing Prof. Ravi Manjithaya, Prof. Sheeba Vasu, and Dr. Kushagra Bansal passively taught me how to ask questions. My enthusiasm for research was also strengthened by Akshaya Nambiar at JNCASR, and Prof. Chandan Goswami and Dr. Tusar Kanta Acharya at NISER, both of whom have had profound impacts with respect to science and kindness.
How do you intend to help Indian science improve?
Indian science is at a great level now, with exciting new research happening all around. Contributing to the academic community in India by being a research faculty is an exciting prospect in itself. However, a bridge between fundamental and clinical research is something that is going to be important to take our work from bench to bedside.
Reference:
Chakraborty, R. et al., Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-Synuclein and mitochondria, Cell Death and Disease, 2023 https://www.nature.com/articles/s41419-023-05835-8
Edited by: Nivedita Kamath
Biopatrika: Bringing Science to Society
© Biopatrika 2023 All Rights Reserved.