Mazzanti Cinthia M, Spanevello Roselia, Ahmed Musthaq, Pereira Luciane B, Gonçalves Jamile F, Corrêa Maisa, Schmatz Roberta, Stefanello Naiara, Leal Daniela B R, Mazzanti Alexandre, Ramos Adriano T, Martins Tessie B, Danesi Cristiane Cademartori, Graça Dominguita L, Morsch Vera M, Schetinger Maria Rosa C
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcellos, 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil.
Int J Dev Neurosci. 2009 Feb;27(1):73-80. doi: 10.1016/j.ijdevneu.2008.09.005. Epub 2008 Sep 27.
The ethidium bromide (EB) demyelinating model was associated with vitamin E (Vit E) and ebselen (Ebs) treatment to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC) and erythrocytes. Rats were divided into seven groups: I-Control (saline), II-(canola); III-(Ebs), IV-(Vit E); V-(EB); VI-(EB+Ebs) and VII-(EB+Vit E). At 3 days after the EB injection, AChE activity in the CC and HC was significantly reduced in groups III, IV, V, VI and VII (p<0.05) and in the ST it was reduced in groups III and V (p<0.05) when compared to the control group. At 21 days after the EB injection, AChE activity in the CC was significantly reduced in groups III, IV and V, while in groups VI and VII a significant increase was observed when compared to the control group. In the HC and ST, AChE activity was significantly reduced in groups V, VI and VII when compared to the control group (p<0.05). In the erythrocytes, at 3 days after the EB injection, AChE activity was significantly reduced in groups III, IV, V, VI and VII and at 21 days there was a significant reduction only in groups VI and VII (p<0.05) when compared to the control group. In conclusion, this study demonstrated that Ebs and Vit E interfere with the cholinergic neurotransmission by altering AChE activity in the different brain regions and in the erythrocytes. Furthermore, treatment with Vit E and Ebs protected against the demyelination lesion caused by EB. In this context, we can suggest that ebselen and Vit E should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with demyelinating events.
将溴化乙锭(EB)脱髓鞘模型与维生素E(Vit E)和依布硒啉(Ebs)治疗相结合,以评估纹状体(ST)、海马体(HP)、大脑皮层(CC)和红细胞中的乙酰胆碱酯酶(AChE)活性。将大鼠分为七组:I-对照组(生理盐水),II-(菜籽油);III-(Ebs),IV-(Vit E);V-(EB);VI-(EB+Ebs)和VII-(EB+Vit E)。在注射EB后3天,与对照组相比,III、IV、V、VI和VII组的CC和HC中的AChE活性显著降低(p<0.05),III和V组的ST中的AChE活性降低(p<0.05)。在注射EB后21天,III、IV和V组的CC中的AChE活性显著降低,而与对照组相比,VI和VII组则显著增加。在HC和ST中,与对照组相比,V、VI和VII组的AChE活性显著降低(p<0.05)。在红细胞中,注射EB后3天,III、IV、V、VI和VII组的AChE活性显著降低,21天时,与对照组相比,仅VI和VII组有显著降低(p<0.05)。总之,本研究表明,Ebs和Vit E通过改变不同脑区和红细胞中的AChE活性来干扰胆碱能神经传递。此外,Vit E和Ebs治疗可预防EB引起的脱髓鞘病变。在此背景下,我们可以认为依布硒啉和Vit E应被视为在与脱髓鞘事件相关的脑部疾病中有待研究的潜在治疗方法和科学工具。