Institute of
bioorganic chemistry

Reactive oxygen species (ROS) are considered a primary source of damage during an ischemic stroke. Studies on this subject are usually performed on either cell culture or animal models, which can make it difficult to translate the results to humans. Currently, 3D neurospheroids derived from induced pluripotent stem cells (iPSCs) are proposed as an optimal alternative for modeling disease conditions. Researchers from the IBCh RAS and other Russian institutions report live imaging of hydrogen peroxide dynamics during the acute phase of hypoxia and reperfusion in human iPSC-derived neural spheroids, stably expressing fluorescent biosensor HyPer7. Contrary to expectations, they demonstrated the absence of ROS overproduction during the ischemia-reperfusion experiment. These results raise concerns about the applicability of such ischemia-reperfusion models due to the lack of a hallmark ROS signature of ischemic stroke. The results are published in Free Radical Biology and Medicine. Learn more

Scientists from the IBCh RAS in collaboration with colleagues from other institutes have delved into the intricate cellular changes occurring in the brains of aging adults. The results of the study challenges existing paradigms by uncovering distinct responses to aging in astrocytes and neurons. Key findings include a significant decrease in the amount of reduced mitochondrial cytochromes in astrocytes, signaling potential mitochondrial dysfunction linked to aging. Notably, this phenomenon was not observed in neurons, highlighting cell-specific nuances in the aging process. The findings pave the way for a more nuanced understanding of the aging process, considering cell-type-specific responses within the brain active milieu. The results are published in Nature Communications. Learn more

The external application of dsRNAh has recently been developed as a new approach for crop protection. It is assumed that the mechanism of dsRNA-mediated antivirus RNA defence is similar to that of natural RNA interference (RNAi). There is, however, no direct evidence to support this idea. Scientists from the IBCh RAS in collaboration with colleagues from JHI (UK) we carried out the analysis of small RNAs (sRNA) as hallmarks of RNAi induced by potato virus Y (PVY). In contrast to PVY-induced production of discrete 21 and 22 nt sRNA species, the externally administered PVY dsRNA led to generation of a non-canonical pool of sRNAs, which were present as ladders of ~18-30 nt in length; suggestive of an unexpected sRNA biogenesis. These findings may have significant implications for further developments in dsRNA-mediated crop protection. The results are published in the International Journal of Molecular Sciences. Learn more

A team of scientists from the IBCh RAS, Lomonosov Moscow State University and other Russian institutes studied the differences in the redox state of neonatal and adult rat cardiomyocytes under hypoxic conditions. Using the highly sensitive HyPer7 biosensor, authors found that hypoxia causes an increase in H2O2 production in adult cardiomyocytes, while neonatal cells, on the contrary, experience a decrease in basal H2O2 levels under the same conditions. This finding correlates with other data obtained by the authors using Raman microspectroscopy, which demonstrate a marked difference in the properties of the mitochondrial electron transport chain of adult and neonatal cells. In particular, in adult cardiomyocytes, hypoxia causes the significant increase in the respiratory chain loading with electrons, while in neonatal cells this effect is not observed. The work was published in Free Radical Biology and Medicine journal. Learn more

Transient or persistent perturbations of the balance between quiescence and division of the hippocampal stem cells due to a brain pathology or therapy can lead to unfavorable long-term outcomes such as premature depletion of their pool, decreased neuronal renewal, and cognitive deficit. Here, using a recently developed method for detection of de novo dividing cells, the members of the redox biology group and the laboratory of molecular technologies from the Department of Metabolism and Redox Biology, IBCH RAS, in the collaboration with colleagues from IHNA&NPh revealed that long-term stimulation of divisions of quiescent stem cells led to premature exhaustion of their pool and that aging of the brain modulates the ability of the quiescent stem cells to be recruited into the cell cycle by pro-neurogenic stimuli. Results of the study have a number of implications for the practical assessment of drugs and treatments with respect to their action on quiescent stem cells at different stages of life in animal preclinical studies. The work is published in the Molecular Neurobiology.