Institute of Biomedical and Biomolecular Science (IBBS)
Making Sense of Glia
Our research centres on glial cells. Glia are the most abundant cells in the brain. They provide neurones with a stable environment in which to function and have critical roles in all brain diseases. Any strategy which aims to promote brain repair will involve glia and will need an understanding of their neuroprotective and neurodestructive functions (Verkhratsky & Butt, 2007. Glial Neurobiology: A Textbook, Wiley, Chichester).
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Glia are the most abundant cells in the brain. |
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Glia - more than glue
The name glia comes from the Greek for glue, and is based on the historical concept that glia are the connective tissue of the brain. However, glia are multifunctional and dynamic cells. The main glial cell types in the CNS are astrocytes, oligodendrocytes, and newly discovered NG2-glia.
Oligodendrocytes and Multiple Sclerosis
Oligodenrocytes are specialised to myelinate axons and facilitate rapid saltatory conduction - their loss underlies the debilitating clinical signs of Multiple Scelrosis (MS). We are examining the role of fibroblast growth factor (FGF2) and intracellular kinase pathways in the regulation of myelination, funded by the Multiple Sclerosis Society.
Astrocytes and Potassium Regulation
Astrocytes provide physical and metabolic support for neurons, and regulate brain levels of ions and neurotransmitters. We are examining the role of Kir4.1 channels in potassium regulation and glial differentiation.
NG2-glia as multipotent neural stem cells NG2-glia are capable of self-renewal and can regenerate oligodendrocytes and possibly neurones. Currently, we are isolating NG2-glia from white matter tissue and determining their multipotency in cell culture. NG2-glia form exquisite contacts with neurons at synapses and nodes of Ranvier and respond to neuronal activity. We are investigating the role of glutamate in regulating the differentiation of NG2-glia.
Breaching the glial barrier to regeneration Regeneration in the CNS is blocked by inhibitory factors expressed by glia, and one of the most potent is NG2, chondroitin sulphate proteoglycan. Modulation of the glial scar therefore has the potential to promote regeneration in the CNS. However, NG2 and other glial molecules, such as semaphorins and tenascins, are repulsive-guidance molecules, and preservation of the glial scaffold and their guidance cues is a prerequisite for directional axon regeneration and functional recovery. To this end, we are investigating the interactions between NG2-glia and regenerating axons following disinhibition, funded by the International Spinal Research Trust.
Sense and Sensibility
Glia sense neuronal activity via their receptors, ion channels and transporters, which have dual roles in physiology and pathology. For example, a principal glial channel is Kir4.1, which we show is critical for myelination and regulation of brain potassium. Regulation of potassium and glutamate levels in the brain are critical functions of astrocytes, and when these glial regulatory mechanisms are impaired, neurones are susceptible to hyperexcitability and degeneration. Glia signal to each other via calcium waves which serve to couple glial regulatory mechanisms to neuronal activity. Disruption of glial regulatory mechanisms results in loss of neuronal function and neurodegeneration, as observed in ischemia, stroke, MS and CNS injury.
Glia sense neuronal activity via their receptors, ion channels and transporters, which have dual roles in physiology and pathology. For example, a principal glial channel is Kir4.1, which we show is critical for myelination and regulation of brain potassium. Regulation of potassium and glutamate levels in the brain are critical functions of astrocytes, and when these glial regulatory mechanisms are impaired, neurones are susceptible to hyperexcitability and degeneration. Glial sensibility is normally coupled to neuronal activity by neurotransmitters, which mediate calcium signals in glia, but enhanced activation disrupts glial neuroprotective functions and results in neurodestruction. Controlling glial functions are therefore key targets in any disease. Our strategy is to understand these mechanisms, using a combined calcium imaging, electrophysiological, and molecular biological approach.Glia signal to each other via calcium waves which serve to couple glial regulatory mechanisms to neuronal activity. Disruption of glial regulatory mechanisms results in loss of neuronal function and neurodegeneration, as observed in ischemia, stroke, MS and CNS injury.