Dr Ragnhildur Thóra Káradóttir
Neurotransmitter signalling to central nervous system progenitor cells
Laboratory: Cambridge Stem Cell Institute, Gleeson Building
Departmental Affiliation: Veterinary Medicine
Ragnhildur Thóra Káradóttir graduated with a degree in Biochemistry from the University of Iceland in 2000. She then completed a four-year Wellcome Trust PhD in Neuroscience at UCL under the supervision of Prof. David Attwell. She continued working with Prof. Attwell as a postdoctoral researcher, before being awarded a Royal Society Dorothy Hodgkin Research Fellowship which she used to work with Prof. Charles ffrench-Constant at the University of Cambridge.
In 2008 she established her own independent research group in Cambridge and in 2011 she was awarded the Wellcome Trust Research Career Development fellowship.
She is currently an editor for the journal Brain Plasticity and a guest editor for Neuroscience and for Neuropharmacology.
- 2006 Doctor of Philosophy (PhD) in Neuroscience from University of London.
- Thesis title: Neurotransmitter signalling to oligodendrocytes
- 2001 Admission to the 4 year PhD Programme in Neuroscience at University College London
- 2000 BSc in Biochemistry from the University of Iceland, 1st Class. Research project: Role of melatonin in Seasonal Affective Disorder
- 2011 Wellcome Trust Career Development Research Fellow
- 2007 Dorothy Hodgkin Research Fellow of the Royal Society held in Dept. of Veterinary Medicine University of Cambridge
- 2006 Postdoctoral research fellow with Prof. David Attwell, Dept. Physiology University College London
- 2001- Wellcome Trust PhD student on 4 year PhD in Neuroscience, Department of Physiology 2005 University College London
CurePSP, Paul G Allen Family Foundation, Lister Institute, MNI McGill-Cambridge collaboration, Wellcome, BBSRC
White matter in a dish! Myelinating co-culture where oligodendrocyte precursor cells (that are plated on top of DRG axons) differentiate into myelinating oligodendrocytes (green; MBP) that myelinate the DRG axons (red; neurofilament). Credit Kimberley Evans
The CNS white matter links billions of neurons in the grey matter. Its function depends on oligodendrocytes enwrapping neuronal axons with myelin to synchronize and increase information flow between neurons: essential for our cognitive abilities, our perception of the world and our motor skills. The importance of myelin becomes evident in diseases, such as multiple sclerosis, where myelin damage leads to cognitive and motor disability. Moreover, recent magnetic resonance imaging and genome-wide association studies have highlighted the contribution of myelin to many diseases that were previously considered ‘neuronal’ like dementia, schizophrenia, autism and bipolar disorder. However, unique to the CNS, myelin regeneration can occur spontaneously in demyelinating disease, as adult oligodendrocyte precursor cells (OPCs; a CNS stem cell that comprises 5% of all cells in the brain) respond to the demyelinating injury and differentiate into new myelinating oligodendrocytes. However, this process often fails, making OPCs differentiation an important therapeutic target.
We have previously shown that OPCs express neurotransmitter receptors and receive synaptic inputs from neuronal axons in the white matter, hence are capable of sensing changes in neuronal activity. The lab’s interest is to understand how signals from neurons induce OPCs to differentiate and myelinate axons during development and with normal ageing; this also could be an underlying mechanism for white matter plasticity.
The devastating consequences of dys/demyelination, in diseases like cerebral palsy, spinal cord injury and multiple sclerosis makes it important to study how OPCs differentiation is regulated. We are actively investigating how OPCs respond to myelin injury and whether neuronal activity and neurotransmitter signalling may regulate the myelin repair process. Our ultimate aim is to find new treatments for white matter disease.
Sylvia Agathou, Kimberley Evans, Mariann Kovacs (Visitor), Deborah Kronenberg-Versteeg, Moritz Matthey, Claudia Pama, Balazs Varga, Katrin Volbracht.
For our brain to work, fast electrical communication between nerve cells is essential. This is achieved by insulating the nerves with a fatty substance called myelin. In diseases like multiple sclerosis, spinal cord injury and stroke, myelin is lost, while in cerebral palsy myelin fails to develop. Lack of myelin causes physical and mental disability. Myelin is provided by cells called oligodendrocytes, which develop from oligodendrocyte precursor cells (OPCs). In the adult, OPCs can repair myelin, but this repair often fails for reasons currently unknown. OPCs can also develop into other types of brain cell, including nerve cells, but it is not known what controls this choice of cell identity. We study how OPCs generate myelin during development and in disease. By investigating how signals in the cells’ environment interact with the properties of the OPCs to instruct them to migrate, generate myelin-making oligodendrocytes, or develop into other brain cells. The aim of this work is to understand how OPCs decide to become myelinating cells, how we can influence them to repair myelin in disease.
- Gautier HO, Evans K, Lundgaard I, James F, Lao-Peregrin C, Franklin RJM, Káradóttir R (2015). Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors. Nature Communications 6: 8518. PMCID:PMC4600759
- Lundgaard I, Luzhynskaya A, Stockley JH, Wang Z, Evans KA, Swire M, Volbracht K, Gautier HO, Franklin RJM, ffrench-Constant C, Attwell D, Káradóttir R (2013). Neuregulin and BDNF induce a switch to NMDA receptor dependent myelination by oligodendrocytes. PLoS Biol. 11(12): e1001743. PMCID:PMC3876980
- Káradóttir R, Hamilton N, Bakiri Y & Attwell D (2008). Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter. Nature Neuroscience 11(4): 450-456. PMCID:PMC2615224
- 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. PMCID:PMC2682777
- Káradóttir R, Cavalier P, Bergersen LH, Attwell D (2005). NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438: 1162-1166. PMCID:PMC1416283