Réus Gislaine Zilli, Bernardini Dos Santos Maria Augusta, Abelaira Helena Mendes, Maciel Amanda Luis, Arent Camila Orlandi, Matias Beatriz Iladi, Bruchchen Lívia, Ignácio Zuleide Maria, Michels Monique, Dal-Pizzol Felipe, Carvalho André Ferrer, Zugno Alexandra Ioppi, Quevedo João
Laboratory of Neurosciences, University of Southern Santa Catarina, Criciuma, SC, 88806-000, Brazil.
Curr Neurovasc Res. 2016;13(2):107-14. doi: 10.2174/1567202613666160219115832.
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.
本研究旨在探讨抗氧化剂N-乙酰半胱氨酸（NAC）和去铁胺（DFX）治疗对糖尿病大鼠脑内细胞内信号通路的影响。为开展本研究，我们通过单次注射四氧嘧啶诱导Wistar大鼠患糖尿病，之后用NAC或DFX对大鼠进行14天的治疗。治疗结束后，测定前额叶皮质（PFC）、海马体、杏仁核和伏隔核（NAc）中c-Jun氨基末端激酶（JNK）、丝裂原活化蛋白激酶-38（MAPK38）、脑源性神经营养因子（BDNF）以及蛋白激酶A和C（PKA和PKC）的免疫含量。DFX治疗增加了糖尿病大鼠PFC和NAc中的JNK含量。在杏仁核中，用生理盐水或NAC治疗的糖尿病大鼠JNK增加。对照大鼠以及用NAC或DFX治疗的糖尿病大鼠PFC中的MAPK38降低；所有组的NAc中MAPK38也降低。DFX治疗使PFC中的PKA降低。在杏仁核中，与对照组相比，用生理盐水或NAC治疗的糖尿病大鼠PKA含量增加；与用生理盐水治疗的糖尿病动物相比，NAC或DFX治疗组的PKA含量降低。在NAc中，用NAC治疗的糖尿病大鼠PKA增加。用NAC治疗的糖尿病大鼠杏仁核中的PKC增加。在PFC中，糖尿病大鼠经DFX治疗后BDNF水平降低。糖尿病大鼠海马体中的BDNF水平降低。然而，DFX治疗可逆转这种效应。在杏仁核中，DFX使非糖尿病大鼠的BDNF增加。在NAc中，DFX治疗增加了糖尿病大鼠的BDNF水平。总之，糖尿病和抗氧化剂治疗均能够以脑区和治疗依赖的方式改变参与细胞存活调节的细胞内信号通路。
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