Ragnhildur Thora Karadottir
Tel.: +44 (0)1223 765860
My research interests are neurotransmitter signalling to oligodendrocytes and their progenitor cells (a type of CNS stem cell), in both health and disease.
For our brain to work, fast communication between nerves is essential. This is achieved by insulating the nerves with myelin. In many neurological diseases myelin is lost, i.e multiple sclerosis, spinal cord injury and stroke. Since myelin occurs throughout the CNS, its loss leads to physical and/or mental disability. Interestingly there exist stem cells, called oligodendrocyte precursor cell (OPC) that develops into myelin making oligodendrocyte during development and in the adult OPCs can carry out myelin repair. However, this repair often fails for reasons currently unknown.
In this project we study how OPCs generate oligodendrocytes during both development and in disease to try to understand why this process can fail in disease.
For the first part of our project we have shown that myelination during development can be switched from a default myelination programme to a more efficient myelination programme that depends on nerve communications, by a growth factor. Now we are studying if myelin repair depends on nerve communications or not, this work might shed a light of the failure of repair seen in disease.
This work should give some clues about how OPCs decide to become myelinating cells and how we can influence them to repair in disease.
Oligodendrocytes wrap around axons in the CNS producing myelin, which speeds the propagation of the action potential. When the myelin sheath is lost, in diseases like cerebral palsy, spinal cord injury and multiple sclerosis, it causes mental and physical disability.
I use patch-clamping and imaging to study how oligodendrocytes respond to neurotransmitters released from axons, both in the normal brain and in pathological conditions. Using this approach, I have shown that NMDA receptors play a key role in causing the damage caused to myelin in disease states.
Oligodendrocyte precursor cells (OPCs) comprise 5% of the cells in the adult brain, where they are the most proliferative cell present. They can generate both neurons and glial cells, making them an important stem cell population in the adult brain.
I have shown that these cells fall into two
classes, with distinct physiological properties.
My future work will focus on the role of oligodendrocyte neurotransmitter receptors and the two classes of OPC in normal myelination and in remyelination after injury.
- Robin Franklin, University of Cambridge
- David Attwell, UCL
- Charles ffrench-Constant, University of Edinburgh
- Bill Richardson, UCL
- Bakiri, Y., D. Attwell and R. Karadottir (2009). Electrical signalling properties of oligodendrocyte precursor cells. Neuron Glia Biol: 1-9. [PubMed]
- Káradóttir R, Bakiri Y, Hamilton N & Attwell D (2008). Spiking and non spiking classes of oligodendrocyte precursor glia in CNS white matter. Nature Neuroscience 11(4): 450-456. [PubMed]
- Kolodziejczyk, K., N. B. Hamilton, A. Wade, R. Karadottir and D. Attwell (2009). The effect of N-acetyl-aspartyl-glutamate and N-acetyl-aspartate on white matter oligodendrocytes. Brain. 132(6):1496-508. [PubMed]
- Bakiri Y, Burzomato V, Frugier G, Hamilton N, Káradóttir R & Attwell D (2008). Glutamatergic signalling in the brain’s white matter. Neuroscience 58(1):266-74. [PubMed]
- Bakiri Y, Hamilton N, Káradóttir R & Attwell D (2008). NMDA receptor block as a therapeutic strategy for reducing ischaemic damage to oligodendrocytes. Glia 56(2):233-40. [PubMed]
- Káradóttir R & Attwell D (2007). Neurotransmitter receptors in the life and death of oligodendrocytes. Neuroscience 145(4): 1426-1438. [PubMed]
- Káradóttir R & Attwell D (2006) Combining patch-clamping of cells in brain slices with immunocytochemical labelling to define cell type and developmental stage. Nature Protocols 1(4), 1977-1985. [PubMed]
- Pattinson D, Baccei M, Káradóttir R, Torsney C, Moss A, McCutcheon J, Giese KP & Fitzgerald M (2006). Aberrant dendritic branching and sensory inputs in the superficial dorsal horn of mice lacking CaMKIIalpha autophosphorylation. Mol Cell Neurosci 33(1): 88-95. [PubMed]
- Káradóttir R, Cavalier P, Bergersen LH & Attwell D (2005). NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438: 1162-1166. [PubMed]
- Allen N*, Káradóttir R* & Attwell D (2005). A preferential role for glycolysis in preventing the anoxic depolarization of rat hippocampal area CA1 pyramidal cells. Journal of Neuroscience 25: 848-859. *Equal 1st author [PubMed]
- Allen N, Káradóttir R & Attwell D (2004). Reversal or reduction of glutamate and GABA transport in CNS pathology and therapy. Pflugers Arch 449: 132-142. [PubMed]