title: Topographical Distribution of Morphological Changes in a Partial Model of Parkinson's Disease--Effects of Nanoencapsulated Neurotrophic Factors Administration.
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.
authors.affiliation: Laboratory of Clinical and Experimental Neuroscience (LaNCE), Department of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Vizcaya, Spain, catalina.requejo@ehu.es.
authors.forename: C
authors.initials: C
authors.lastname: Requejo
authors.forename: J A
authors.initials: JA
authors.lastname: Ruiz-Ortega
authors.forename: H
authors.initials: H
authors.lastname: Bengoetxea
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Blanco
authors.forename: E
authors.initials: E
authors.lastname: Herrán
authors.forename: A
authors.initials: A
authors.lastname: Aristieta
authors.forename: M
authors.initials: M
authors.lastname: Igartua
authors.forename: L
authors.initials: L
authors.lastname: Ugedo
authors.forename: J L
authors.initials: JL
authors.lastname: Pedraz
authors.forename: R M
authors.initials: RM
authors.lastname: Hernández
authors.forename: J V
authors.initials: JV
authors.lastname: Lafuente
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004261:DNA Replication; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D015552:Injections, Intralesional; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D053769:Nanocapsules; D009419:Nerve Tissue Proteins / Q000032:analysis; D009457:Neuroglia / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D009479:Neuropeptides / Q000032:analysis; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D053769:Nanocapsules; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D042461:Vascular Endothelial Growth Factor A; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase