title: Antioxidant Therapy Alters Brain MAPK-JNK and BDNF Signaling Path-ways in Experimental Diabetes Mellitus.
abstract: This study was designed to investigate the effects of treatment with the antioxidants N-acetylcysteine (NAC) and deferoxamine (DFX) in intracellular pathways in the brain of diabetic rats. To conduct this study we induced diabetes in Wistar rats with a single injection of alloxan, and afterwards rats were treated with NAC or DFX for 14 days. Following treatment completion, the immunocontent of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase-38 (MAPK38), brain-derived neurotrophic factor (BDNF), and protein kinases A and C (PKA and PKC) were determined in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens (NAc). DFX treatment increased JNK content in the PFC and NAc of diabetic rats. In the amygdala, JNK was increased in diabetics treated with saline or NAC. MAPK38 was decreased in the PFC of control and in diabetic rats treated with NAC or DFX; and in the NAc in all groups. PKA was decreased in the PFC with DFX treatment. In the amygdala, PKA content was increased in diabetic rats treated with either saline or NAC, compared to controls; and it was decreased in either NAC or DFX-treated groups, compared to saline-treated diabetic animals. In the NAc, PKA was increased in NAC-treated diabetic rats. PKC was increased in the amygdala of NAC-treated diabetic rats. In the PFC, the BDNF levels were decreased following treatment with DFX in diabetic rats. In the hippocampus of diabetic rats the BDNF levels were decreased. However, treatment with DFX reversed this effect. In the amygdala the BDNF increased with DFX in non-diabetic rats. In the NAc DFX treatment increased the BDNF levels in diabetic rats. In conclusion, both diabetes and treatment with antioxidants were able to alter intracellular pathways involved in the regulation of cell survival in a brain area and treatment-dependent fashion.
authors.affiliation: Laboratory of Neurosciences, University of Southern Santa Catarina, Criciuma, SC, 88806-000, Brazil. gislainezilli@hotmail.com.
authors.forename: Gislaine Zilli
authors.initials: GZ
authors.lastname: Réus
authors.forename: Maria Augusta
authors.initials: MA
authors.lastname: Bernardini Dos Santos
authors.forename: Helena Mendes
authors.initials: HM
authors.lastname: Abelaira
authors.forename: Amanda Luis
authors.initials: AL
authors.lastname: Maciel
authors.forename: Camila Orlandi
authors.initials: CO
authors.lastname: Arent
authors.forename: Beatriz Iladi
authors.initials: BI
authors.lastname: Matias
authors.forename: Lívia
authors.initials: L
authors.lastname: Bruchchen
authors.forename: Zuleide Maria
authors.initials: ZM
authors.lastname: Ignácio
authors.forename: Monique
authors.initials: M
authors.lastname: Michels
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: André Ferrer
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Alexandra Ioppi
authors.initials: AI
authors.lastname: Zugno
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D003676:Deferoxamine; D000111:Acetylcysteine