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Link to original content: https://doi.org/10.1038/nature05865
‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease | Nature
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‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease

Nature volume 447, pages 1081–1086 (2007)Cite this article

Abstract

Why dopamine-containing neurons of the brain’s substantia nigra pars compacta die in Parkinson’s disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Cav1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson’s disease. These mechanisms remain latent in adulthood, and blocking Cav1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking (‘rejuvenation’) protects these neurons in both in vitro and in vivo models of Parkinson’s disease, pointing to a new strategy that could slow or stop the progression of the disease.

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Figure 1: SNc dopaminergic neurons are Ca v1.3-Ca 2+-channel-dependent pacemakers.
Figure 2: Pacemaking mechanisms in SNc dopaminergic neurons are developmentally regulated and sensitive to Ca v1.3 deletion.
Figure 3: Cav1.3 channel blockade induces a reversion to a juvenile form of Na+ /HCN-channel-dependent pacemaking.
Figure 4: Pacemaking currents govern dendritic Ca2+ concentrations.
Figure 5: Rejuvenation of SNc dopaminergic neurons protects them against the mitochondrial toxin rotenone and chronic MPTP treatment.

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Acknowledgements

This work was supported by grants from the Picower Foundation and NIH NINDS to D.J.S. and G.E.M. We thank J. Held, D. Wokosin, P. Hockberger, E. Mugnaini, S. Ulrich, K. Saporito, Q. Ruan, J. Jackolin, F. Jodelka and M. Avram for help with this work.

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  1. Caroline Rick

    Present address: Present address: BCTU, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.,

Authors and Affiliations

  1. Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA,

    C. Savio Chan, Jaime N. Guzman, Ema Ilijic, Jeff N. Mercer, Caroline Rick, Tatiana Tkatch & D. James Surmeier

  2. Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, Chicago, Illinois 60064, USA,

    Gloria E. Meredith

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Chan, C., Guzman, J., Ilijic, E. et al. ‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease. Nature 447, 1081–1086 (2007). https://doi.org/10.1038/nature05865

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