Presymptomatic MPTP Mice Show Neurotrophic S100B/mRAGE Striatal Levels

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Viana, SD (Author) Other; Fernandes, RC (Author) Other; Canas, PM (Author) Other; Silva, AM (Author) Other; Felix Carvalho (Author) FFUP; Ali, SF (Author) Other; Fontes Ribeiro, CAF (Author) Other; Pereira, FC (Author) Other

Journal

Title: CNS Neuroscience & Therapeutics

Vol. 22

Pages: 396-403

ISSN: 1755-5930

Publisher: Wiley

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-00K-ET9

DOI: 10.1111/cns.12508

Abstract (EN): AimsAstrocytic 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. MethodsC57BL/6 mice were submitted to a chronic MPTP paradigm (20mg/kg i.p., 2 i.d-12h apart, 5days/week for 2weeks) and euthanized 7days 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). ResultsThis 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. ConclusionOur 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8