title: Presymptomatic MPTP Mice Show Neurotrophic S100B/mRAGE Striatal Levels.
abstract: OBJECTIVE
  Astrocytic S100B and receptor for advanced glycation endproducts (RAGE) have been implicated in Parkinson׳s disease (PD) pathogenesis through yet unclear mechanisms. This study attempted to characterize S100B/mRAGE (signaling isoform) axis in a dying-back dopaminergic (DAergic) axonopathy setting, which mimics an early event of PD pathology.
  
  
  METHODS
  C57BL/6 mice were submitted to a chronic MPTP paradigm (20 mg/kg i.p., 2 i.d-12 h apart, 5 days/week for 2 weeks) and euthanized 7 days posttreatment to assess mRAGE cellular distribution and S100B/mRAGE density in striatum, after probing their locomotor activity (pole test and rotarod). Dopaminergic status, oxidative stress, and gliosis were also measured (HPLC-ED, WB, IHC).
  
  
  RESULTS
  This MPTP regimen triggered increased oxidative stress (augmented HNE levels), gliosis (GS/Iba1-reactive morphology), loss of DAergic fibers (decreased tyrosine hydroxylase levels), and severe hypodopaminergia. Biochemical deficits were not translated into motor abnormalities, mimicking a presymptomatic PD period. Remarkably, striatal neurotrophic S100B/mRAGE levels and major neuronal mRAGE localization coexist with compensatory responses (3-fold increase in DA turnover), which are important to maintain normal motor function.
  
  
  CONCLUSIONS
  Our findings rule out the involvement of S100B/mRAGE axis in striatal reactive gliosis, DAergic axonopathy and warrant further exploration of its neurotrophic effects in a presymptomatic compensatory PD stage, which is a fundamental period for successful implementation of therapeutic strategies.
authors: Laboratory of Pharmacology and Experimental Therapeutics/IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI - University of Coimbra, Coimbra, Portugal.|Instituto Politécnico de Coimbra, ESTESC-Coimbra Health School, Farmácia, Portugal.
authors: Sofia D
authors: SD
authors: Viana
authors: Laboratory of Pharmacology and Experimental Therapeutics/IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI - University of Coimbra, Coimbra, Portugal.
authors: Rosa C
authors: RC
authors: Fernandes
authors: Laboratory of Pharmacology and Experimental Therapeutics/IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI - University of Coimbra, Coimbra, Portugal.
authors: Paula M
authors: PM
authors: Canas
authors: Laboratory of Pharmacology and Experimental Therapeutics/IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI - University of Coimbra, Coimbra, Portugal.
authors: Andréa M
authors: AM
authors: Silva
authors: UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors: Félix
authors: F
authors: Carvalho
authors: Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR, USA.
authors: Syed F
authors: SF
authors: Ali
authors: Laboratory of Pharmacology and Experimental Therapeutics/IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI - University of Coimbra, Coimbra, Portugal.
authors: Carlos A
authors: CA
authors: Fontes Ribeiro
authors: Laboratory of Pharmacology and Experimental Therapeutics/IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CNC.IBILI - University of Coimbra, Coimbra, Portugal.
authors: Frederico C
authors: FC
authors: Pereira
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D018476:Hypokinesia / Q000473:pathology / Q000503:physiopathology; D020267:MPTP Poisoning / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D045442:Rotarod Performance Test; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000067759:Receptor for Advanced Glycation End Products; D064568:S100 Calcium Binding Protein beta Subunit; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; C027576:4-hydroxy-2-nonenal; D004298:Dopamine
keywords: MPTP; Presymptomatic; RAGE; S100B; Striatum