Yu. A. Panina’s research while affiliated with Krasnoyarsk State Medical University and other places

The NLRP3 inflammasome is known to play a significant role in the development of neurodegeneration and physiological aging, as well as the development of metabolic inflammation, which has generated significant interest in the scientific community in finding effective inhibitors of the NLRP3 inflammasome and assessing their effects. The purpose of this study was to evaluate the effect of pharmacological modulation of NLRP3 activity using an indirect NLRP3 inflammasome inhibitor, glibenclamide, on the expression of metaflammasome components in in vitro brain cells obtained from middle-aged mice. The study revealed that glibenclamide reduces the expression of pro-inflammatory markers NLRP3 and IL18 in cell culture, which in turn leads to the prevention of phosphorylation of protein kinases of the metaflammasome complex – PKR and IKKβ. However, we did not observe changes in the expression of pathologically phosphorylated IRS, as well as in the number of senescent cells in cultures after the exposure to glibenclamide.

Early life stress is an important factor predisposing to the development of pathology of the nervous system in animals and humans in the late period of ontogenesis. We used an early life stress model to assess the activation of the piriform cortex upon presentation of olfactory stimuli in experimental animals (CD1 mice, P60 and 10 months old) as well as to assess the expression of markers of neurons with prolonged immaturity involved in the processes of plasticity of the adult brain and its recovery. We found that early life stress reduces the number of immature neurons with the DCX+PSA-NCAM+ phenotype in the piriform cortex and the response to olfactory memory induction. In addition, olfactory stimulation reduces sensitivity to unpleasant stimuli at a young age (P60), stimulates short-term memory. However, at the age of 10 months, these effects are less evident. The results obtained indicate a possible contribution of immature neurons of the piriform cortex to the mechanisms of aberrant neuroplasticity after early life stress.

Autism is a neurodevelopment disorder with impaired social communication and stereotypical behavior. Olfactory stimulation has interesting eff ects. By using the olfactory stimulation we can change social behavior and anxiety in mice.

The role and morphological features of microglia (M1 and M2 microglia, "stellate", "amoeboid", giant, round-shaped, rod-shaped, dysfunctional, etc.) in vivo under physiological conditions and during the development of neurodegenerative diseases have been described. Various methods and techniques of microglia isolation from adult (density gradient isolation, use of "magnetic beads", from mesenchymal bone marrow progenitor cells) and newborn (obtaining from a mixed glial culture, density gradient isolation) animals have been considered, including microglia isolation from the cerebral cortex or hippocampus. Various methods of cell cultivation have been shown, including obtaining two-dimensional and three-dimensional cell cultures (on scaffolds, hydrogels, nanofibers), co-cultures on slice cultures of the hippocampus, as well as changes in microglia during cultivation.

Pathologies associated with perinatal exposure of the CNS to damaging factors, including hypoxia, are a serious problem. However, the mechanisms by which they influence the development of brain damage have been insufficiently studied. The purpose of this study is to analyze the BBB permeability and expression of markers of its structural and functional integrity in animals with hypoxia (rats subjected to hypoxia at the age of P7) at the early (1 hour after the hypoxia) and delayed (P28) periods of their development. In sections of the rat brains, we immunohistochemically evaluated the expression of HIF-1 and Rac1; the Evans blue dye content was measured by the photometric method in the brain homogenates. In animals subjected to hypoxia, BBB permeability increased, CD31 expression was reduced, RAC1 expression increased, HIF-1-positive cells were retained in the hippocampus mainly at the early stage of development; CD31 and RAC1 expression was suppressed during the delayed period of development. The most-pronounced brain damage at the age of P7 corresponds to changes in the structural and functional integrity and permeability of the BBB; the recovery of a neurological deficit and the permeability of the BBB (at the age of P28) under damage to the brain corresponds to the period of reparative angiogenesis, as well as manifestations of HIF-1 effects in endothelial cells and astrocytes in the cortex and limbic system.

This literature review demonstrates the importance and consequences of early life stress for the development of the brain and its role in the formation of neurological and mental illnesses (particularly depression). The most dangerous is chronic early life stress during the neonatal period of development in the first days after birth, when the effects on the development of the brain, neuro-, synapto-, and glio-, and angiogenesis are the most stable. Among all the neuropsychological effects of early life stress, the most common are apparent as depressive disorders in humans and animals, and this constitutes a widely used model of experimental depression in rodents.

The expression of thrombospondin-1 (TS-1) and its receptors CD47 and CD36 in the cerebral cortex and hippocampus of rats under damaging factors in the early postnatal period was studied. After hypoxia on the 7th day of postnatal development, an increase in the number of CD47-expressing cerebral endothelial cells (days of postnatal development: P28–P70) and reduction in the number of TS-1-expressing astrocytes in the cortex at P28 were observed. In animals subjected to early postnatal stress at the age of P2–P15, a decrease in TS-1-expressing astrocytes in the cortex and hippocampus was registered (predominantly at the age of P28). It was noted that these changes characterize the period of long-term effects (P28–P70) of early stress that is relevant to the processes of reparative angiogenesis and arresting of neurological deficits.