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Deleterious Effects of VEGFR2 and RET Inhibition in a Preclinical Model of Parkinson’s Disease

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A Correction to this article was published on 05 March 2018

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Abstract

Neurotrophic factors (NTFs) are a promising therapeutic option for Parkinson’s disease (PD). They exert their function through tyrosine kinase receptors. Our goal was to assess the effects of administering a selective tyrosine kinase inhibitor (vandetanib) that blocks VEGFR2 and RET receptors in a preclinical model of PD. Rats underwent intrastriatal injections of 6-hydroxydopamine (6-OHDA). Two weeks later, the rats received 30 mg/kg vandetanib or saline orally. The effects were assessed using the rotational behavioral test, tyrosine hydroxylase (TH) immunohistochemistry, and western blot. In 6-OHDA-lesioned rats, motor symptoms were almost undetectable, but morphological and biochemical changes were significant. Vandetanib treatment, combined with the presence of 6-OHDA lesions, significantly increased behavioral impairment and morphological and biochemical changes. Therefore, after vandetanib treatment, the TH-immunopositive striatal volume, the percentage of TH+ neurons, and the extent of the axodendritic network in the substantia nigra decreased. Glial fibrillary acidic protein-positivity significantly decreased in the striatum and substantia nigra in the vandetanib-treated group. In addition, p-Akt and p-ERK 1/2 levels were significantly lower and caspase-3 expression significantly increased after vandetanib administration. In conclusion, we demonstrate for the first time the deleterious effect of a tyrosine kinase inhibitor on the dopaminergic system, supporting the beneficial and synergistic effect of NTFs reported in previous papers.

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  • 05 March 2018

    The authors found a terrible mistake in the manuscript. The legends from the Fig. 5 and 6 are interchanged. The Fig. 5 should be appeared with the legend from the Fig. 6 and Fig. 6 should be appeared with the legend from the Fig. 5.

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Acknowledgments

The authors appreciate the support from the University of the Basque Country (UPV/EHU) (UFI 11/32), the Basque Government (GIC IT 901/16 and 747-13, PPG 17/51), “Ministerio de Ciencia e Innovación” SAF 2016-77758-R (AEI/FEDER, UE), and SGIker (UPV/EHU). C. Requejo appreciates the UPV/EHU for a fellowship subvention.

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Authors and Affiliations

  1. LaNCE, Department of Neuroscience, University of the Basque Country (UPV/EHU), Vizcaya, Leioa, Spain

    C. Requejo, H. Bengoetxea, S. Bulnes & J. V. Lafuente

  2. Department of Pharmacology, University of the Basque Country (UPV/EHU), Vizcaya, Leioa, Spain

    J. A. Ruiz-Ortega & L. Ugedo

  3. Nanoneurosurgery Group, BioCruces Health Research Institute, 48903, Barakaldo, Bizkaia, Spain

    J. V. Lafuente

  4. Faculty of Health Science, Universidad Autónoma de Chile, Santiago de Chile, Chile

    J. V. Lafuente

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  1. C. Requejo
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  2. J. A. Ruiz-Ortega
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  3. H. Bengoetxea
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Correspondence to C. Requejo.

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A correction to this article is available online at https://doi.org/10.1007/s12035-018-0979-y.

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Requejo, C., Ruiz-Ortega, J.A., Bengoetxea, H. et al. Deleterious Effects of VEGFR2 and RET Inhibition in a Preclinical Model of Parkinson’s Disease. Mol Neurobiol 55, 201–212 (2018). https://doi.org/10.1007/s12035-017-0733-x

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