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Ragnhildur Thóra Káradóttir

Regulation of myelin formation, plasticity and regeneration

myelination in cerebelllum
The brain's superhighway

The CNS white matter links billions of neurons in the grey matter. Its function depends on oligodendrocytes enwrapping neuronal axons with myelin to synch

ronize and increase information flow between neurons: essential for our cognitive abilities, our perception of the world and our motor skills. The importance
of myelin is evident in disease, as when damaged it leads to both mental and physical disability.   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 neuronal activity.  The lab’s interest is to understand how synaptic inputs 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. 

human IPSC
Human stem cells
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.

Key Publications

Neuronal activity regulates remyelination via glutamate signaling to oligodendrocyte progenitors.  Gautier HO, Evans K, Lundgaard I, James F, Lao-Peregrin C, Franklin RJM & Káradóttir R (2015).  Nature Communications 6: 8518. 

Neuregulin and BDNF induce a switch to NMDA receptor dependent myelination by oligodendrocytesLundgaard 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). PLoS Biology 11(12):e1001743. 

Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter. Káradóttir R*, Hamilton N, Bakiri Y &Attwell D (2008). Nature Neuroscience 11(4): 450-456

Combining patch-clamping of cells in brain slices with immunocytochemical labelling to define cell type and developmental stage. Káradóttir R & Attwell D (2006). Nature Protocols 1(4): 1977-1985.

NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Káradóttir R, Cavalier P, Bergersen LH & Attwell D (2005).  Nature 438: 1162-1166. 

Ragnhildur Thora Karadottir

Dr Ragnhildur Thóra Káradóttir

Reader in Cellular Neuroscience

rk385@cam.ac.uk

Group members:  Dr Deborah Kronenberg-Versteeg, Dr. Balazs Varga, Dr. Mathew Horrocks, Miss Sylvia Agathou, Miss Katrin Volbracht, Ms Kimberley Evans, Mr. Moritz Matthey, Miss Claudia Pama, Miss Migle Apanaviciute


    Plain English

    Half of the human brain is white matter, its function depends on oligodendrocytes wrapping myelin around neuronal axons. Oligodendrocytes develop from stem cells called oligodendrocyte precursor cells (OPCs). 

    Myelin profoundly affects our cognitive abilities by dramatically decreasing the time needed to pass information between brain areas. Myelin also mediates faster control of our muscles and makes it possible for us to see, and hear, and even learn new skills. Accordingly, significant mental or physical impairment ensues when myelin fails to develop or when it is disrupted. Myelin repair can occur spontaneously as OPCs respond to lesions and differentiate into new myelin-producing oligodendrocytes. However, this repair process often fails, leading to neuronal death.

    The focus of Karadottir’s lab is to understand how myelin is formed through out life and how myelin repair can be promoted in disease.

    Funding

    Wellcome Trust

    Paul G. Allen Family foundation

    CurePSP

    MS Society

    BBSRC

    The Lister Institute of Preventive Medicine

    Thóra is available for consultancy.

    Thóra is accepting application for PhD students.