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Topographical Distribution of Morphological Changes in a Partial Model of Parkinson’s Disease—Effects of Nanoencapsulated Neurotrophic Factors Administration

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Abstract

Administration of various neurotrophic factors is a promising strategy against Parkinson’s disease (PD). An intrastriatal infusion of 6-hydroxidopamine (6-OHDA) in rats is a suitable model to study PD. This work aims to describe stereological parameters regarding rostro-caudal gradient, in order to characterize the model and verify its suitability for elucidating the benefits of therapeutic strategies. Administration of 6-OHDA induced a reduction in tyrosine hidroxylase (TH) reactivity in the dorsolateral part of the striatum, being higher in the caudal section than in the rostral one. Loss of TH-positive neurons and axodendritic network was highly significant in the external third of substantia nigra (e-SN) in the 6-OHDA group versus the saline one. After the administration of nanospheres loaded with neurotrophic factors (NTF: vascular endothelial growth factor (VEGF) + glial cell line-derived neurotrophic factor (GDNF)), parkinsonized rats showed more TH-positive fibers than those of control groups; this recovery taking place chiefly in the rostral sections. Neuronal density and axodendritic network in e-SN was more significant than in the entire SN; the topographical analysis showed that the highest difference between NTF versus control group was attained in the middle section. A high number of bromodeoxyuridine (BrdU)-positive cells were found in sub- and periventricular areas in the group receiving NTF, where most of them co-expressed doublecortin. Measurements on the e-SN achieved more specific and significant results than in the entire SN. This difference in rostro-caudal gradients underpins the usefulness of a topological approach to the assessment of the lesion and therapeutic strategies. Findings confirmed the neurorestorative, neurogenic, and synergistic effects of VEGF + GDNF administration.

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Acknowledgments

The authors thank the support of the University of the Basque Country (UPV/EHU) (UFI 11/32), the Basque Government (Saiotek SA-2010/00028, GIC 794/13, IT 747/13), “Ministerio de Ciencia e Innovación” (SAF2010-20375), FEDER funds and SGIker (UPV/EHU). C. Requejo appreciates the UPV/EHU for a fellowship subvention.

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Authors and Affiliations

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

    C. Requejo, H. Bengoetxea, A. Garcia-Blanco & J. V. Lafuente

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

    J. A. Ruiz-Ortega, A. Aristieta & L. Ugedo

  3. NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria, Alava, Spain

    E. Herrán, M. Igartua, J. L. Pedraz & R. M. Hernández

  4. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Alava, Spain

    E. Herrán, M. Igartua, J. L. Pedraz & R. M. Hernández

  5. Group Nanoneurosurgery, Institute of Health Research Biocruces, Barakaldo, Spain

    J. V. Lafuente

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  1. C. Requejo
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  2. J. A. Ruiz-Ortega
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  11. J. V. Lafuente
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Correspondence to C. Requejo.

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Requejo, C., Ruiz-Ortega, J.A., Bengoetxea, H. et al. Topographical Distribution of Morphological Changes in a Partial Model of Parkinson’s Disease—Effects of Nanoencapsulated Neurotrophic Factors Administration. Mol Neurobiol 52, 846–858 (2015). https://doi.org/10.1007/s12035-015-9234-y

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