Journal article
Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors
E Hedlund, L Belnoue, S Theofilopoulos, C Salto, C Bye, C Parish, Q Deng, B Kadkhodaei, J Ericson, E Arenas, T Perlmann, A Simon
Scientific Reports | NATURE PORTFOLIO | Published : 2016
DOI: 10.1038/srep26448
Abstract
Degeneration of dopamine neurons in the midbrain causes symptoms of the movement disorder, Parkinson disease. Dopamine neurons are generated from proliferating progenitor cells localized in the embryonic ventral midbrain. However, it remains unclear for how long cells with dopamine progenitor character are retained and if there is any potential for reactivation of such cells after cessation of normal dopamine neurogenesis. We show here that cells expressing Lmx1a and other progenitor markers remain in the midbrain aqueductal zone beyond the major dopamine neurogenic period. These cells express dopamine receptors, are located in regions heavily innervated by midbrain dopamine fibres and their..
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Funding Acknowledgements
We would like to thank D Berg for exploratory experiments in the initial phase of this study. This work was funded by grants from the Swedish Research Council, AFA Insurances, Cancerfonden and the European Research Council to A.S. The European Union, Seventh Framework Programme (mdDANeurodev), Swedish Strategic Research Foundation and Knut and Alice Wallenberg Foundation to T.P. The Swedish Research Council (VR projects: DBRM, 2008-2811, 2011-3116 and 2011-3318), Swedish Strategic Research Foundation (SRL program), European Commission (NeuroStemcell) and Karolinska Institutet (SFO Thematic Center in Stem cells and Regenerative Medicine) to E.A. Swedish Medical Research Council (2011-2651) and NEURO Sweden to E.H. L.B. was supported by a postdoc fellowship from Wenner-Gren Foundation, Sweden. C.P. was supported by a senior medical research fellowship from the Viertel charitable foundation, Australia. C.B. was supported by a Peter Doherty Fellowship from the National Health and Medical Research Council, Australia. Human post mortem tissues were kindly received from the National Disease Research Interchange (NDRI; www.ndriresource.org). We would like to thank Shanzheng Yang for help with the microphotographs of the midbrain cultures (E.A.).