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Research Groups

Staffan Cullheim, M.D., Ph.D.

Staffan Cullheim

Staffan Cullheim, M.D., Ph.D.

Research Focus

We have earlier described the ability of mammalian motoneurons to regenerate their axons after lesion, and related it to morphological and chemical changes in these cells. We are now focussing our studies towards a hallmark response of a neuron to an axon lesion, i.e. the elimination of synaptic connections with injured cells, the synaptic stripping response. In a recent study of gene-modified mice, lacking the ability to present antigen by use of the MHC class I system, we have shown that in such mice there is a much larger elimination of synapses after axon lesion, and the regenerative capacity is lower. This is the first time immune molecules have been directly linked to synaptic plasticity following injury in the nervous system.

Our aim is now to identify the exact nature of the MHC class I molecules and their receptors responsible for the synaptic effects, and whether they are found in neurons or glial cells, which have been attributed key roles for the synaptic elimination. The possibility that another set of immune molecules, complement proteins, are important tagging molecules for synapses selected for elimination will also be tested. The studies are done together with a number of very well established researchers, where our own competence in light and electron microscopy, immunohistochemistry, quantitative in situ hybridization and cell culture techniques is complemented with immunological, as well as cell and molecular biological knowledge in other groups.

Selected Publications

Thams S, Oliveira A, Cullheim S.

MHC class I expression and synaptic plasticity after nerve lesion.

Brain Research Review 57: 265-269, 2008

Wallquist W, Plantman S, Thams S, Thyboll J, Kortesmaa J, Lännergren J, Domogatskaya A, Ögren SO, Risling M, Hammarberg H, Tryggvason K, Cullheim S.

Impeded interaction between Schwann cells and axons in the absence of laminin ±4.

Journal of Neuroscience 25: 3692-3700, 2005.

Oliveira AL, Thams S, Lidman O, Piehl F, Hökfelt T, Kärre K, Lindå H, Cullheim S.

A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy.

Proceedings of the National Academy of Science U.S.A. 101: 17843-17848. 2004.

Hammarberg H, Lidman O, Lundberg C, Eltayeb SY, Gielen AW, Muhallab S, Svenningsson A, Lindå H, van Der Meide PH, Cullheim S, Olsson T, Piehl F.

Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells.

Journal of Neuroscience 20: 5283-5291, 2000

Lindå H, Hammarberg H, Cullheim S, Levinovitz A, Khademi M, Olsson T.

Expression of MHC class I and beta2-microglobulin in rat spinal motoneurons: regulatory influences by IFN-gamma and axotomy.

Experimental Neurology 150: 282-295, 1998