Pharmacological correction of the apoptosis level in cortical neurons of ageing HER2/neu transgenic mice
| Autor: | Yu. O. Kozlova, D. S. Sukhanov, V. N. Anisimov, E. D. Bazhanova, D. L. Teply |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse medicine.medical_specialty TUNEL assay Physiology Transgene Neurodegeneration Biology medicine.disease Biochemistry Neuroprotection HER2/neu 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Ageing Apoptosis Internal medicine medicine biology.protein 030217 neurology & neurosurgery Ecology Evolution Behavior and Systematics |
| Zdroj: | Journal of Evolutionary Biochemistry and Physiology. 52:64-73 |
| ISSN: | 1608-3202 0022-0930 |
| DOI: | 10.1134/s0022093016010075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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