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Sci Rep. 2016 Jun 1;6:26448. doi: 10.1038/srep26448.

Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors.

Author information

1
Ludwig Institute for Cancer Research, Stockholm Branch, Nobels v 3, 171 77 Stockholm, Sweden.
2
Department of Neuroscience, Karolinska Institutet, Retzius v. 8, 171 77 Stockholm, Sweden.
3
Department of Cell and Molecular Biology, Karolinska Institutet, von Eulers v. 3, 171 77 Stockholm, Sweden.
4
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Retzius v. 8, 171 77 Stockholm, Sweden.
5
Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, 3010 Australia.

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 proliferation can be stimulated by antagonizing dopamine receptors, ultimately leading to increased neurogenesis in vivo. Furthermore, treatment with dopamine receptor antagonists enhances neurogenesis in vitro, both from embryonic midbrain progenitors as well as from embryonic stem cells. Altogether our results indicate a potential for reactivation of resident midbrain cells with dopamine progenitor potential beyond the normal period of dopamine neurogenesis.

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