Pharmacological correction of the apoptosis level in cortical neurons of ageing HER2/neu transgenic mice

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• 作者：E. D. Bazhanova ; Yu. O. Kozlova…
• 关键词：cytoflavin ; piracetam ; apoptosis ; neurons ; sensorimotor cortex ; HER2/neu transgenic mice
• 刊名：Journal of Evolutionary Biochemistry and Physiology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：52
• 期：1
• 页码：64-73
• 全文大小：197 KB
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• 作者单位：E. D. Bazhanova (1)
  Yu. O. Kozlova (1)
  V. N. Anisimov (2)
  D. S. Sukhanov (3)
  D. L. Teply (4)
  
  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia
  2. Petrov Research Institute of Oncology, St. Petersburg, Russia
  3. Mechnikov North-West State Medical University, St. Petersburg, Russia
  4. Astrakhan State University, Astrakhan, Russia
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Evolutionary Biology
  Biochemistry
  Animal Physiology
  Russian Library of Science
  
• 出版者：MAIK Nauka/Interperiodica distributed exclusively by Springer Science+Business Media LLC.
• ISSN：1608-3202

文摘

Neurodegenerative changes and neuronal death underlie ageing of the nervous system. We investigated the mechanisms of apoptosis in sensorimotor cortical neurons of HER2/neu transgenic mice during ageing, as well as the functional changes in the cortex and the involvement of exogenous neurometabolites (cytoflavin, piracetam) in the regulation of neuronal death and locomotor and psycho-emotional status in mice. The level of apoptosis and expression of the apoptotic protein markers (TUNEL, immunohistochemistry, Western blotting) were detected in HER2/neu transgenic mice versus wild type mice (FBV strain). In ageing wild type mice, the basal activity decreases while the anxiety level increases correlating with the high level of neuronal apoptosis. We revealed specific behavioral features of HER2/neu transgenic mice—their low basal activity which remains intact during ageing. Previously, we have shown that in this mouse strain the level of apoptosis is low, with no age-related dynamics, due to the suppression primarily of the p53-dependent pathway by HER2 (tyrosine kinase receptor) overexpression. Here we show that cytoflavin and piracetam have a pronounced neuroprotective effect, preserving and restoring the nervous system functions (improving locomotion and psychological status) in both mouse strains. The effect of the tested neurometabolites on neuronal apoptosis is ambiguous. In case of low-level apoptosis, there occurs its moderate stimulation in HER2/neu transgenic mice that are characterized by a high level of carcinogenesis (via the extrinsic and p53-dependent pathways with caspase-3 activation) which probably prevents tumor development. By contrast, in aged wild-type mice there is a marked decrease in the level of age-related apoptosis (via the stimulation of antiapoptotic protein Mcl-1 expression) supposed to prevent neurodegeneration.