Regulation of striatal astrocytic receptor for advanced glycation end-products variants in an early stage of experimental Parkinson's disease

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Viana, SD (Autor) Outra; Valero, J (Autor) Outra; Rodrigues Santos, P (Autor) Outra; Couceiro, P (Autor) Outra; Silva, AM (Autor) Outra; Felix Carvalho (Autor) FFUP; Ali, SF (Autor) Outra; Fontes Ribeiro, CA (Autor) Outra; Pereira, FC (Autor) Outra

Revista

Título: Journal of Neurochemistry

Vol. 138

Páginas: 598-609

ISSN: 0022-3042

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 6 Citações

Scopus - 12 Citações

Outras Informações

ID Authenticus: P-00K-R50

DOI: 10.1111/jnc.13682

Abstract (EN): Convincing evidence indicates that advanced glycation end-products and danger-associated protein S100B play a role in Parkinson's disease (PD). These agents operate through the receptor for advanced glycation end-products (RAGE), which displays distinct isoforms playing protective/deleterious effects. However, the nature of RAGE variants has been overlooked in PD studies. Hence, we attempted to characterize RAGE regulation in early stages of PD striatal pathology. A neurotoxin-based rodent model of PD was used in this study, through administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6 mice. Animals were killed 6h post-MPTP to assess S100B/RAGE contents (RT-qPCR, ELISA) and RAGE isoform density (WB) and cellular distribution (immunohistochemistry). Dopaminergic and gliotic status were also mapped (HPLC-ED, WB, immunohistochemistry). At this preliminary stage of MPTP-induced PD in mice, RAGE inhibitory isoforms were increased whereas full-length RAGE was not affected. This putative cytoprotective RAGE phenotype paired an inflammatory and pro-oxidant setting fueling DAergic denervation. Increased RAGE inhibitory variants occur in astrocytes showing higher S100B density but no overt signs of hypertrophy or NF-B activation, a canonical effector of RAGE. These findings expand our understanding of the toxic effect of MPTP on striatum and offer first invivo evidence of RAGE being a responder in early stages of astrogliosis dynamics, supporting a protective rather tissue-destructive phenotype of RAGE in the initial phase of PD degeneration. These data lay the groundwork for future studies on the relevance of astrocytic RAGE in DAergic neuroprotection strategies.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12