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Adult neurogenesis in Parkinson’s disease

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Abstract

Parkinson’s disease (PD), the second most common neurodegenerative disorder, affects 1–2 % of humans aged 60 years and older. The diagnosis of PD is based on motor symptoms such as bradykinesia, rigidity, tremor, and postural instability associated with the striatal dopaminergic deficit that is linked to neurodegenerative processes in the substantia nigra (SN). In the past, cellular replacement strategies have been evaluated for their potential to alleviate these symptoms. Adult neurogenesis, the generation of new neurons within two proliferative niches in the adult brain, is being intensively studied as one potential mode for cell-based therapies. The subventricular zone provides new neurons for the olfactory bulb functionally contributing to olfaction. The subgranular zone of the hippocampus produces new granule neurons for the dentate gyrus, required for memory formation and proper processing of anxiety provoking stimuli. Recent years have revealed that PD is associated with non-motor symptoms such as hyposmia, anhedonia, lack of novelty seeking behavior, depression, and anxiety that are not directly associated with neurodegenerative processes in the SN. This broad spectrum of non-motor symptoms may partly rely on proper olfactorial processing and hippocampal function. Therefore, it is conceivable that some non-motor deficits in PD are related to defective adult neurogenesis. Accordingly, in animal models and postmortem studies of PD, adult neurogenesis is severely affected, although the exact mechanisms and effects of these changes are not yet fully understood or are under debate due to conflicting results. Here, we review the current concepts related to the dynamic interplay between endogenous cellular plasticity and PD-associated pathology.

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Acknowledgments

This study was supported by the Bavarian State Ministry of Sciences, Research and the Arts, ForNeuroCell (J.W.; Erlangen, Germany), the Elite Network Bavaria (F.M., M.R., J.W.), and the Adalbert-Raps-Foundation (J.W.). F.M. is supported by the Interdisciplinary Center for Clinical Research (IZKF) Erlangen. The authors thank Julius Ecke for the graphic artwork.

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None of the author has to declare a conflict of interest.

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Authors and Affiliations

  1. Department of Molecular Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany

    Franz Marxreiter, Martin Regensburger & Jürgen Winkler

  2. Department of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany

    Franz Marxreiter & Martin Regensburger

  3. Department of Neurosciences, University of California, San Diego 9500 Gilman Drive, La Jolla, CA, 92093-0662, USA

    Jürgen Winkler

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  1. Franz Marxreiter
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Correspondence to Jürgen Winkler.

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Marxreiter, F., Regensburger, M. & Winkler, J. Adult neurogenesis in Parkinson’s disease. Cell. Mol. Life Sci. 70, 459–473 (2013). https://doi.org/10.1007/s00018-012-1062-x

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  • DOI: https://doi.org/10.1007/s00018-012-1062-x

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