Phenotypic and functional plasticity of glial cells under neuroinflammation: potential implications for brain repair
Submission Deadline: 31 Mar 2022
Guest Editors
Adjunct Prof. Jagdeep K. Sandhu
National Research Council Canada, University of Ottawa
Interests: My research is focused on understanding the effects of an excessive inflammatory environment in neurodegenerative diseases. I have spent the last two decades at the forefront of Parkinson’s disease research, particularly in demonstrating the importance of oxidative stress and inflammation in the development and progression of this disease. My work has revealed the importance of astroglia and the astroglial glutathione antioxidant system as well as glia-derived neurotrophic growth factor in neuronal health and demise. Currently, I am leading the research dedicated to better understanding of CNS innate immune responses. An improved understanding of the CNS innate immunity might be followed by the development of glia-based therapeutic strategies. In line with this, I am developing blocking/neutralizing single-domain antibodies (also known as nanobodies) against the death domains of the NLRP3 inflammasome (dysregulated in microglia), for the treatment of Parkinson’s disease, possibly other diseases with a similar component of inflammation.
Emeritus Researcher Marianna Sikorska-Walker
National Research Council Canada
Interests: Throughout my scientific career I was and continue to be interested in understanding the molecular mechanisms that control and allow to maintain physiological cellular phenotypes. My scientific journey took me through the fields of cell physiology, oncology, molecular cell biology, neurobiology and neuropathology. I have carried out studies on the regulation of cell proliferation, neoplastic transformation, cell signaling, chromatin structure and transcriptional regulation of gene expression, cell death mechanisms and the methods to prevent it, especially in the CNS. I have developed and patented a technology to generate water-dispersible nanomicellar formulations of water-insoluble lipophilic substances (the Ubisol technology) allowing the controlled delivery of therapeutic dosages of natural substances with biological activities, such as polyphenols and coenzyme Q10. I have directed studies at multiple centers to evaluate the therapeutic efficacy of Ubisol-Q10, which holds a great promise to halt the progression of neurodegeneration.
Special Issue Information
Dear Colleagues,
Astroglia and microglia, are the non-neuronal cells in the mammalian central nervous system (CNS). For a long time glial cells were considered as glue/supporting cells, however it has increasingly become clear that glial cells are active players in brain development and function. Astroglia are the star-shaped cells that are involved in the maintenance of CNS homeostasis by regulating the blood-brain barrier integrity and cerebral blood flow, providing antioxidant and trophic factor support, uptake and recycling of neurotransmitters as well as detoxification of reactive oxygen and nitrogen species. Astrocytes also provide metabolic support to neurons and regulate short- and long-term plasticity and memory formation. Microglia are the resident immune cells in the brain parenchyma that play a crucial role in immune surveillance and maintenance of neuronal health. As cellular sensors and effector cells of the CNS, they possess an array of receptors that detect pathological stimuli and are responsible for elimination of the injurious stimuli and restoration of CNS homeostasis.
Although earlier studies were focused on the phenotypic alterations of glial cells, newly developed technologies, such as next generation RNA sequencing and spatial transcriptomics have revealed heterogeneous populations of ‘homeostatic glia’ and ‘reactive/activated’ glia that has unique ‘molecular signatures’ and perform distinct functions. Glial cells are wired in distinct neural circuits and dysfunction or death of glial cells results in the disruption of these networks, in turn, leading to neuronal cell death. Glial cell dysfunction is associated with an increased production of pathological levels of proinflammatory cytokines and chemokines and development of several age-related neurodegenerative diseases. Taken together, it is evident that both astroglia and microglia are crucial players in supporting neuronal survival and proper functioning of neural circuits and high order brain function.
This special issue is dedicated to the plasticity of glial cells under neuroinflammation and possibility to exploit and refocus their function on brain repair mechanisms. We are seeking authors to contribute original research and/or review articles that will discuss how dysfunction of glial cells can result in neuroinflammation, loss of blood-brain (BBB) integrity, failure of neural networks and neuronal cell death. Furthermore, we highly encourage the submission of articles dealing with therapeutic targeting of glia.
Suggested Topics:
1. Role of glia in the regulation of neurovascular unit and BBB integrity
2. Role of glia in synaptogenesis and synapse protection
3. Role of glia in autophagy and cell death
4. Role of glia in antigen presentation and mobilization of immune cells
5. Role of glial ion channels and transporters in brain function and disease
6. Molecular phenotyping of glial cells
7. Methods to monitor glial function
8. Glial cell senescence
9. Glial scaring in neurological disorders
10. Therapeutic targeting of glia
Adjunct Prof. Jagdeep K. Sandhu and Marianna Sikorska-Walker
Guest Editors
Keywords
- Astroglia
- Microglia
- Neuron-glia Interactions
- Neurovascular Unit
- Blood-brain Barrier
- Cytokines and Chemokines
- Innate Immunity
- Toll-like Receptors
- Inflammasomes
- Synaptogenesis
- Synaptic Dysfunction
- Neuroinflammation
- Oxidative Stress
- Brain Repair
- Glia-based Therapeutics
Published Paper (1)
Glial Glutamate Transporter-Mediated Plasticity: System xc-/xCT/SLC7A11 and EAAT1/2 in Brain Diseases
Front. Biosci. (Landmark Ed) 2023, 28(3), 57; https://doi.org/10.31083/j.fbl2803057
(This article belongs to the Special Issue Phenotypic and functional plasticity of glial cells under neuroinflammation: potential implications for brain repair)