Research interests have included monoamine neurons, development, growth factors, regeneration, aging, transplantation in the central nervous system, models for Parkinson’s disease and its treatment, models for spinal cord injury and treatment strategies, the roles of transcription factors in the nervous system, genetic risk factors for Parkinson’s disease, and the Nogo signaling system. We showed that transplantation of embryonic dopamine neurons can counteract Parkinson’s disease in an animal model, and demonstrated functional effects of a repair strategy for complete spinal cord injury in an adult mammal.
Present focus is aging, neurodegenerative diseases, particularly Parkinson’s disease, the role of the Nogo system in the formation of lasting memories and treatment strategies for spinal cord injury. We have recently found that oral treatment with the clinically used cancer drug Imatinib improves recovery in an animal model of traumatic spinal cord injury. Recent studies of the mtDNA mutator mouse have shown that maternally inherited mtDNA mutations can cause mild aging phenotypes and aggravate premature aging phenotypes in mice carrying mutated PolgA genes.
We have recently shown how several genes encoding proteins belonging to the nerve growth inhibitory Nogo signaling system are regulated to influence structural synaptic plasticity and the formation of lasting memories. Ongoing studies using transgenic animals aim at understanding molecular mechanisms behind the formation of lasting memories and causes of memory disorders, as seen e.g. in aging.
Overexpression of Nogo receptor 1 (NgR1) in forebrain neurons does not affect gross brain anatomy but inhibits the formation of dendritic spines. To the left are shown ex vivo diffusion tensor imaging (DTI) to detect white matter tracts in control (top) and NgR1 overexpressing (bottom) brains. To the right are examples of Golgi-stained dendrites from control (left Golgi image) and NgR1 overexpressing (right Golgi image) animals. Shown are distal dendrites from neurons in the cingulate cortex. NgR1 overexpression causes significant alterations of mature spine densities and dendritic architecture in a brain-area specific manner. From Karlsson et al Cerebral Cortex 2016.
NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity.
Cereb. Cortex 2016 Apr;26(4):1804-17
Dopamine Is Required for the Neural Representation and Control of Movement Vigor.
Cell 2015 Sep;162(6):1418-30
Germline mitochondrial DNA mutations aggravate ageing and can impair brain development.
Nature 2013 Sep;501(7467):412-5
Imatinib enhances functional outcome after spinal cord injury.
PLoS ONE 2012 ;7(6):e38760
Impaired mitochondrial transport and Parkin-independent degeneration of respiratory chain-deficient dopamine neurons in vivo.
Proc. Natl. Acad. Sci. U.S.A. 2011 Aug;108(31):12937-42
Tobias Karlsson - Postdoc
Emma Arvidsson - Postdoc
Katrin Wellfelt - Laboratory manager
Margareta Widing - Biomedical scientist
Gabriella Smedfors - PhD Student
Alvin Brodin - R&D trainee