Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of parkinson's disease
✍ Scribed by Göran Bertilsson; Cesare Patrone; Olof Zachrisson; Annica Andersson; Karin Dannaeus; Jessica Heidrich; Jarkko Kortesmaa; Alex Mercer; Elisabet Nielsen; Harriet Rönnholm; Lilian Wikström
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 732 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
We investigated the effects of exendin‐4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP‐1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region. In vitro, exendin‐4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule‐associated protein 2, β‐III‐tubulin, and neuron‐specific enolase. When exendin‐4 was given intraperitoneally to naïve rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the number of bromodeoxyuridine‐positive cells and the number of neuronal precursor cells expressing doublecortin were increased. Exendin‐4 was tested in the 6‐hydroxydopamine model of Parkinson's disease to investigate its possible functional effects in an animal model with neuronal loss. After unilateral lesion and a 5‐week stabilization period, the rats were treated for 3 weeks with exendin‐4. We found a reduction of amphetamine‐induced rotations in animals receiving exendin‐4 that persisted for several weeks after drug administration had been terminated. Histological analysis showed that exendin‐4 significantly increased the number of both tyrosine hydroxylase‐ and vesicular monoamine transporter 2‐positive neurons in the substantia nigra. In conclusion, our results show that exendin‐4 is able to promote adult neurogenesis in vitro and in vivo, normalize dopamine imbalance, and increase the number of cells positive for markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's disease. © 2007 Wiley‐Liss, Inc.