title: Age-related neuroinflammation and changes in AKT-GSK-3β and WNT/ β-CATENIN signaling in rat hippocampus.
abstract: Aging is a multifactorial process associated with an increased susceptibility to neurodegenerative disorders which can be related to chronic inflammation. Chronic inflammation, however, can be characterized by the persistent elevated glucocorticoid (GCs) levels, activation of the proinflammatory transcription factor NF-кB, as well as an increase in cytokines. Interestingly, both NF-кB and cytokines can be even modulated by Glycogen Synthase Kinase 3 beta (GSK-3β) activity, which is a key protein that can intermediate inflammation and metabolism, once it has a critical role in AKT signaling pathway, and can also intermediate WNT/β-CATENIN signaling pathway. The aim of this study was to verify age-related changes in inflammatory status, as well as in the AKT and WNT signaling pathways. Results showed an age-related increase in neuroinflammation as indicated by NF-кB activation, TNF-α and GCs increased levels, a decrease in AKT activation and an increase in GSK-3β activity in both 12- and 24- month old animals. Aging also seems to induce a progressive decrease in canonical WNT/β-CATENIN signaling pathway once there is a decrease in DVL-2 levels and in the transcription of Axin2 gene. Little is known about the DVL-2 regulation as well as its roles in WNT signaling pathway, but for the first time it was suggested that DVL-2 expression can be changed along aging.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Ana Maria Marques
authors.initials: AM
authors.lastname: Orellana
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Andrea Rodrigues
authors.initials: AR
authors.lastname: Vasconcelos
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Jacqueline Alves
authors.initials: JA
authors.lastname: Leite
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: de Sá Lima
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Diana Zukas
authors.initials: DZ
authors.lastname: Andreotti
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Carolina Demarchi
authors.initials: CD
authors.lastname: Munhoz
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Elisa Mitiko
authors.initials: EM
authors.lastname: Kawamoto
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000502:physiology; D007249:Inflammation / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: AKT; GCs; GSK-3β; NF-κB; β-catenin