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

• DOI: 10.1007/s12035-015-9234-y
• Publication Date: 2015-06-04T02:05:35Z
• Authors: C. Requejo; J. A. Ruiz-Ortega; H. Bengoetxea; A. Garcia-Blanco; E. Herrán; A. Aristieta; M. Igartua; L. Ugedo; J. L. Pedraz; R. M. Hernández; J. V. Lafuente
• Keywords: DNA Replication; Doublecortin Domain Proteins; Male; Neurons; Doublecortin Protein; Neuropeptides; Drug Synergism; Nerve Tissue Proteins; Injections, Intralesional; Corpus Striatum; Rats; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Nanocapsules; Parkinsonian Disorders; Glial Fibrillary Acidic Protein; Animals; Drug Therapy, Combination; Glial Cell Line-Derived Neurotrophic Factor; Oxidopamine; Microtubule-Associated Proteins; Neuroglia

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.