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First published online 4 July 2007
doi: 10.1242/dev.002329

Development 134, 2881-2887 (2007)
Published by The Company of Biologists 2007
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Midbrain dopaminergic neurogenesis and behavioural recovery in a salamander lesion-induced regeneration model

Clare L. Parish1,*, Anna Beljajeva2,*, Ernest Arenas1,{dagger} and András Simon2,{dagger},{ddagger}

1 Department of Medical Biochemistry and Biophysics, Karolinska Institute, Center of Excellence in Developmental Biology, Stockholm, Sweden.
2 Department of Cell and Molecular Biology, Medical Nobel Institute, Center of Excellence in Developmental Biology, Karolinska Institute, Stockholm, Sweden.

{ddagger} Author for correspondence (e-mail: Andras.Simon{at}ki.se)

Accepted 4 June 2007

Death and lack of functional regeneration of midbrain dopaminergic (DA) neurons, decreased DA input in the target striatum and movement anomalies characterise Parkinson's disease (PD). There is currently no cure for PD. One way to promote recovery would be to induce or enhance DA neurogenesis. Whether DA neurogenesis occurs in the adult midbrain is a matter of debate. Here, we describe the creation of a salamander 6-hydroxydopamine model of PD to examine midbrain DA regeneration. We demonstrate a robust and complete regeneration of the mesencephalic and diencephalic DA system after elimination of DA neurons. Regeneration is contributed by DA neurogenesis, leads to histological restoration, and to full recovery of motor behaviour. Molecular analyses of the temporal expression pattern of DA determinants indicate that the regenerating DA neurons mature along a similar developmental program as their mammalian counterparts during embryogenesis. We also find that the adult salamander midbrain can reactivate radial glia-like ependymoglia cells that proliferate. The salamander model provides insights into the mechanisms of DA regeneration/neurogenesis and may contribute to the development of novel regenerative strategies for the mammalian brain.

Key words: Neurogenesis, Newt, Regeneration, 6-hydroxydopamine, Behaviour, Dopamine, Parkinson's disease






© The Company of Biologists Ltd 2007