Neuropharmacology

Biography

Biography: Bazhanova Elena

Abstract

Age-dependent loss of brain neurons leads to declining cognitive abilities, behavior changing. Actual issue is to provide a new therapeutic strategy for treatment of aging neurodegeneration. Aims of investigation were to study mechanism of neuronal apoptosis in sensorimotor cortex in physiological and pathological aging, and to investigate role of exogenous neurometabolites (angiogen, cytoflavin, piracetam) in regulation of apoptosis and cortex functions in aging. We used HER2/neu transgenic mice, wild-type FVB/N line. We determined apoptosis level and CD95, caspase-8, caspase-3, p53, Bcl-2, Mcl-1, Erk1/2 expression (TUNEL, immunohistochemistry, Western blotting), and psycho-emotional and locomotor status of mice. Locomotor activity decreased and anxiety increased in aged FVB/N, which correlates with the high level of apoptosis. Locomotor activity of HER2/neu is low, and does not change with aging. Apoptosis level is low in this line of mice, and is stable in aging. Cause of it is overexpression of HER2 tyrosine kinase receptor, which supresses p53-dependent pathway. Angiogen, cytoflavin, piracetam have a marked neuroprotective effect on cortex neurons of FVB/N, HER2/neu aged mice. These drugs improved locomotion and psychological status in both mouse strains. The involvement of these drugs in apoptosis regulation depends on biochemical neuron status, which is determined by genetic line. HER2 overexpression alters course of biochemical processes and signaling in cells. Studied neurometabolites have moderate stimulation of apoptosis by extrinsic and p53-dependent pathways in HER2/neu mice. It has clinic significance, because low apoptosis leads to high carcinogenesis. These drugs decrease significant age-dependent apoptosis in wild-type old animals, and this way prevent neurodegeneration.