ABSTRACT
Aims: This study aimed to find the cardiac cells which can participate in the processes of regeneration at patients with heart failure due to ischaemic heart disease. To investigate the participation of myosin activating protein kinases in sarcomerogenesis, because sarcomerogenesis is the crucial part of cardiomyocyte differentiation process. Study Design: Resident cardiomyocyte progenitors and dedifferentiated cardiomyocytes were found in left atrial appendages from patients with heart failure due to ischaemic heart disease. We used a cell model of fetal cardiomyocytes with the disassembly contractile apparatus to study the forming of new myofibrils (or sarcomerogenesis) regulated by myosin activating protein kinases. Place and Duration of Study: Cardiology Research and Production Center, Research Center for Obstetrics, Gynecology and Perinatology, Department of Fundamental and Applied Neurobiology of V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology between June 2014 and October 2015. Methodology: We included 10 patients with heart failure due to ischaemic heart disease. Resident cardiomyocyte progenitors and dedifferentiated cardiomyocytes were found by the immunofluorescence approach and the electron microscopy. To determine the myosin activating protein kinases localization in human fetal cardiomyocytes at the 8-9 week heart gestation stage immunofluorescence approach was used. Results: We detected the cardiomyocyte progenitor cells which express c-Kit and Nkx-2.5, other cells express Mdr-1 and GATA-4. Dedifferentiated cardiomyocytes were found. It has been established that smooth muscle, nonmuscle and skeletal myosin light chain kinases are colocalized with nonmuscle myosin in premyofibrils in fetal human cardiomyocytes. Conclusion: We demonstrated that the heart of patients with heart failure due to ischaemic heart disease contains the progenitor resident cardiomyocytes and dedifferentiated cardiomyocytes. These cardiac cells possibly can proliferate and differentiate to mature cardiomyocytes and recover heart function and structure after injury. Myosin activating protein kinases may contribute in myofibril formation during the cardiomyocyte differentiation.
ABSTRACT
Aims: The aim of our study was to investigate the effects of continuous action of ultrasonic waves of variable frequencies on behavior of rats in "classical" tests used to reveal depression-like behavior, to evaluate the influence of different psychotropic drugs on rates of these tests and to analyze expression of several genes involved in pathogenesis of depression. Study Design: Rats in individual cages were exposed to ultrasonic irradiation for 21 days. Place and Duration of Study: V.P. Serbsky National Recearh Center For Social and Forensic Psychiatry, Department of Basic and Applied Neurobiology, Moscow, Russian Federation, between November 2012 and January 2013. Methodology: 48male non-pedigree albino rats were divided into 5 groups: nonultrasound- saline, ultrasound-saline, ultrasound-fluoxetine, ultrasound-bupropion and ultrasound-tianeptine. After 21 days of irradiation social interaction test, forced swimming test and sucrose preference test (anhedonia test) were conducted. Than rats were decapitated and prefrontal cortex were taken for RT-qPCR gene expression analysis of 5-HT1A, 5-HT2A, 5HT1B, 5HT2B receptors and SERT. Results: Depression-like behavior manifests itself in reduced social activity in social interaction test, increased immobility in forced swimming test and lower sucrose consumption in anhedonia test. The administrated antidepressants demonstrated their effectiveness, except for bupropion in the social interaction test. RT-qPCR gene expression analysis showed reduced expression of 5HT2A receptor gene and increased expression of SERT gene in the prefrontal cortex of rats stressed with ultrasonic radiation. Conclusion: The obtained data allow to conclude that further investigations with lager number of animals, extended tests battery may allow to claim that this model meets the main requirements set to animal models (face, predictive and construct validity) and can be used in studies of depression-like disorders caused by a situation of informational uncertainty and in pre-clinical development of new antidepressants.