Open AccessPresymptomatic MPTP Mice Show Neurotrophic S100B/ mRAGE Striatal Levels
Author(s) -
Viana Sofia D.,
Fernandes Rosa C.,
Canas Paula M.,
Silva Andréa M.,
Carvalho Félix,
Ali Syed F.,
Fontes Ribeiro Carlos A.,
Pereira Frederico C.
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12508
Subject(s) - gliosis , mptp , dopaminergic , striatum , oxidative stress , medicine , tyrosine hydroxylase , glial cell line derived neurotrophic factor , dopamine , neurotrophic factors , endocrinology , neuroscience , parkinson's disease , psychology , receptor , disease
Summary Aims 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 ( DA ergic) axonopathy setting, which mimics an early event of PD pathology. Methods C57 BL /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 DA ergic 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. Conclusion Our findings rule out the involvement of S100B/ mRAGE axis in striatal reactive gliosis, DA ergic 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.