Bazhanova E D, Anisimov V N, Sukhanov D S, Teplyĭ D L
Eksp Klin Farmakol. 2015;78(2):3-9.
The safety of cortical neurons and their functional activity is essential for organism at all stages of ontogenesis. However, aging changes leading to an increase in apoptosis level may cause considerable damage to cerebral cortex function, including sensorimotor. We have studied the role of exogenous neurometabolites (angiogen, cytoflavin) in apoptosis regulation and correction of age-related motor and behavioral disturbances. To study the regulation of neuronal morphofunctional activity, we used accelerate-senescent transgenic HER2 mice in comparison to wild type FBV mice. Functional changes in cerebral cortex were studied by the Suok test and open field test, the level of neuronal apoptosis was assessed by TUNEL method, the expression of apoptosis-modulating proteins was detected by immunohistochemistry and Western blotting. We have revealed differences in psycho-emotional and locomotor activity of these strains of mice. In addition, results of our study showed morphological differences: increase in the apoptosis level of cortical neurons in aged FBV type mice, but no changes in aged HER2 mice. The investigated drugs induce cell death of cortical neurons in transgenic mice of both ages and in young wild-type mice by p53-dependent pathway. Increased apoptosis in the cortex of old transgenic mice has important clinical implications, because reduced apoptosis during aging is one of the causes of cancer. The treatment of old wild-type animals reduces elevated neuronal apoptosis, which decreases risk of age neurodegeneration. Thus, revealed morphological changes in the cerebral cortex are the basis for involutional disabilities (including reduced locomotor activity and increased anxiety level). The use of angiogen and cytoflavin treatment improves functional activity of the cortex and protects normal structure of nervous tissue.
皮质神经元的安全性及其功能活动在个体发育的各个阶段对生物体都至关重要。然而,导致细胞凋亡水平升高的衰老变化可能会对大脑皮质功能造成相当大的损害,包括感觉运动功能。我们研究了外源性神经代谢物(血管生成素、细胞黄素)在细胞凋亡调节以及纠正与年龄相关的运动和行为障碍中的作用。为了研究神经元形态功能活动的调节,我们使用了加速衰老的转基因HER2小鼠,并与野生型FBV小鼠进行比较。通过索克试验和旷场试验研究大脑皮质的功能变化,通过TUNEL法评估神经元凋亡水平,通过免疫组织化学和蛋白质免疫印迹法检测凋亡调节蛋白的表达。我们揭示了这些品系小鼠在心理情绪和运动活动方面的差异。此外,我们的研究结果显示出形态学上的差异:老年FBV型小鼠皮质神经元的凋亡水平增加,但老年HER2小鼠没有变化。所研究的药物通过p53依赖途径诱导两个年龄阶段的转基因小鼠以及年轻野生型小鼠的皮质神经元细胞死亡。老年转基因小鼠皮质中凋亡增加具有重要的临床意义,因为衰老过程中凋亡减少是癌症的原因之一。对老年野生型动物的治疗可降低升高的神经元凋亡,从而降低年龄相关性神经退行性变的风险。因此,所揭示的大脑皮质形态学变化是退行性残疾(包括运动活动减少和焦虑水平增加)的基础。使用血管生成素和细胞黄素进行治疗可改善皮质的功能活动并保护神经组织的正常结构。