Title:Antioxidant Therapy Alters Brain MAPK-JNK and BDNF Signaling Path-ways in Experimental Diabetes Mellitu s
Volume: 13
Issue: 2
Author(s): Gislaine Zilli Réus, Maria Augusta Bernardini dos Santos, Helena Mendes Abelaira, Amanda Luis Maciel, Camila Orlandi Arent, Beatriz Iladi Matias, Lívia Bruchchen, Zuleide Maria Ignácio, Monique Michels, Felipe Dal-Pizzol, André Ferrer Carvalho, Alexandra Ioppi Zugno and João Quevedo
Affiliation:
Keywords:
Antioxidants, JNK, MAPK, BDNF, brain, 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.
