Uspehi fiziologičeskih nauk

Insulin is traditionally considered a hormone of pancreatic origin that regulates glucose homeostasis and a wide range of metabolic and hormonal processes at the periphery. However, in recent decades, convincing evidence has been obtained that insulin also controls many processes in the brain, performing the functions of a neurotrophic factor, neuromodulator and neuroprotector, and some areas of the brain are capable of synthesizing insulin de novo. Insulin implements its effects in the central nervous system through the insulin signaling system, which in its structural and functional organization and regulatory mechanisms has significant similarities with that in the periphery. Since the total pool of insulin in the CNS consists of insulin produced by β-cells and entering the brain through the blood-brain barrier (BBB) and the hormone synthesized by brain structures, a decrease in its production or weakening of its transport through the BBB lead to insulin deficiency in the brain and disruption of its signaling. Other causes of weakened insulin signaling in the brain include central insulin resistance, neuroinflammation caused by increased activity of proinflammatory factors, the development of reactive astrogliosis and activation of microglia, as well as increased activity of enzymes that cause insulin degradation. One of the promising approaches for effective restoration of insulin signaling in the CNS is the use of intranasally administered insulin (IAI), which enters the brain directly through axonal pathways. Currently, IAI is used in the clinic to treat patients with Alzheimer's disease and cognitive deficit associated with type 2 diabetes mellitus (T2DM). However, the therapeutic potential of IAI is not limited to this. We have shown that IAI is effective in correcting metabolic and hormonal disorders associated with T1DM, T2DM, metabolic syndrome and obesity, and a number of its restorative effects are enhanced by the combined use of IAI with metformin, proinsulin C-peptide, and gangliosides, administered both systemically and intranasally. This indicates that the targets of IAI in diabetic pathology and obesity are not only brain structures, but also peripheral organs and tissues, including components of the gonadal and thyroid systems. This review is devoted to the problem of insulin signaling in the brain, its disorders in various pathologies, as well as the use of IAI to restore the activity of the brain's insulin system, including for the purpose of normalizing neurocognitive, metabolic and hormonal indicators in diabetic pathology.

The objective of this review is to present the results of our own studies of neural networks that detect and make decisions when recognizing “everyday” visual targets: faces, letters, text, and order in chaos. Digital methods of image synthesis and processing have made it possible to synthesize calibrated and test image sets that simulate visual scenes. These scenes contain targets and noise with specified statistical, spatial, and temporal characteristics that selectively activate and inhibit modules of large-scale neural networks of the human brain. It is shown how networks representing foveolar and macular vision interact. As a result of the work of opponent neural networks of the prefrontal cortex, decisions are made when recognizing targets. Each of the large-scale neural networks of the brain is involved in various combinations that ensure purposeful human activity. The work of mechanisms of local and global scene analysis when searching for targets is considered: recognition of text, facial expressions, and face rotation, matrices of Gabor elements with varying degrees of ordering. Models of these mechanisms are built on the basis of convolutional, diffusion and generative neural networks. The influence of statistical properties of images and their internal content on decision-making by humans and machines is shown. The ways of development of psychophysiological studies of the organization and activity of large-scale neural networks of the human “visual” system shown.

Due to the development of medicine and the improvement of the standard of living in the world, the proportion of the elderly population is increasing, so the study of the mechanisms of age-related changes in cognitive functions seems to be an urgent task. The purpose of this review is to provide data on the mechanisms of age-related changes in cognitive functions and to draw a conclusion on possible further directions of research in this area. The review presents modern theories of cognitive aging (reserve theory, compensatory theory, frontal lobe aging theory, inhibition deficit theory, sensory deprivation theory). Particular attention is paid to the molecular and genetic aspects of cognitive aging of the brain: the role of DNA integrity disorders and individual characteristics of DNA tandem repeats in connection with the dynamics of cognitive functions and aging of the nervous system are discussed, and the role of gene expression (BDNF, Rag1, APOE, etc.), which are associated with changes in cognitive functions, is considered. The novelty of this work is determined by the reliance on modern scientific literature, which allows us to identify promising areas for further study of the topic. These areas include the study of individual genes and molecular markers in terms of changes in their expression with age (such as mitogens EGF and FGF, neurotrophic factors BDNF, NGF, GDNF, synapsins, Rag1, APOE, etc.) and the study of the role of tandem repeats of the genome, including those located on satellite DNA (not many studies have been devoted to this topic). Understanding the mechanisms of cognitive aging at different levels of the body can contribute to the development of effective methods for the prevention and treatment of cognitive impairment.