Stelmashook Elena V, Voronkov Dmitriy N, Stavrovskaya Alla V, Novikova Svetlana V, Yamshikova Nina G, Olshanskij Artem S, Guschina Anastasiya S, Shedenkova Margarita O, Genrikhs Elizaveta E, Isaev Nickolay K
Research Center of Neurology, Volokolamskoe Shosse 80, 125367 Moscow, Russia.
Research Center of Neurology, Volokolamskoe Shosse 80, 125367 Moscow, Russia; M.V. Lomonosov Moscow State University, Biological Faculty, 119234 Moscow, Russia.
Brain Res. 2023 Apr 15;1805:148290. doi: 10.1016/j.brainres.2023.148290. Epub 2023 Feb 18.
Methylene blue (MB) can be used as a multidirectional neuroprotector to stop the development of multiple cascades of neuron damage during neurodegenerative processes. This study assesses a protective effect of MB, using an experimental simulation of sporadic Alzheimer's disease by intracerebroventricular administration of streptozotocin (STZ) in rats. It was found that a STZ-induced impairment of memory can be partially mitigated with intravenous injections of MB after the administration of STZ. The treatment of animals with MB prevented the STZ-induced increase in the number and density of microglial and GFAP-positive cells in the brain cortex. In addition, it was shown that the expression of the LC3B protein, an indicator of autophagy, increases in the hippocampus of animals treated with STZ. In the hippocampus of animals treated with MB, an increase in the expression of the LC3B protein was prevented. Using the Griess reaction assay and immunocytochemical study was found that MB reduces lipopolysaccharide-induced NO-production and the expression of iNOS in cultured neurons. In conclusion, our data demonstrate that MB has neuroprotective and anti-inflammatory effects and is able to prevent autophagy. These effects have important therapeutic implications, so MB could potentially play a role in the treatment of neurodegenerative processes.
亚甲蓝(MB)可作为一种多向神经保护剂,在神经退行性变过程中阻止神经元损伤的多个级联反应的发展。本研究通过向大鼠脑室内注射链脲佐菌素(STZ)来模拟散发性阿尔茨海默病,评估了MB的保护作用。研究发现,在注射STZ后静脉注射MB可部分减轻STZ诱导的记忆损伤。用MB治疗动物可防止STZ诱导的大脑皮质中小胶质细胞和GFAP阳性细胞数量及密度的增加。此外,研究表明,自噬指标LC3B蛋白在接受STZ治疗的动物海马体中的表达增加。在用MB治疗的动物海马体中,LC3B蛋白的表达增加被阻止。通过格里斯反应测定法和免疫细胞化学研究发现,MB可降低脂多糖诱导的培养神经元中NO的产生及iNOS的表达。总之,我们的数据表明MB具有神经保护和抗炎作用,并且能够预防自噬。这些作用具有重要的治疗意义,因此MB可能在神经退行性变过程的治疗中发挥作用。