Ya. V. Gorina’s research while affiliated with Siberian Federal University and other places

Every year, the number of people diagnosed with Alzheimer’s disease is rapidly increasing. Despite numerous studies, it was not possible to select a therapy that would reliably slow down the course of the disease and result in its complete cure. In this case, any consideration of the issue related to the search for drugs to eliminate cognitive and psychoemotional disorders in Alzheimer’s disease is a pressing problem that deserves special attention. We collected articles from the PubMed database published over the past 10 years. The aim of this review was to analyze the latest experimental data and results regarding the relationship between Alzheimer’s disease and the activity of neuropeptides, such as oxytocin, vasopressin, and neuropeptide S, and describing the effects that occur upon their administration. This will allow for a more complete understanding of the problem and update information on this issue. The ability of neuropeptides to restore impaired cognitive functions in an animal model of Alzheimer’s disease is examined in more detail. Detailed information on the relationship and positive effect of the studied neuropeptides on Alzheimer’s disease allows to consider these neuropeptides as potential drugs for the treatment of this disease.

Behavioral phenotyping of rodents using neurodegeneration models has received much research attention over the past three decades. However, some difficulties still exist in understanding the variability of behavior caused by genetic, environmental, and biological factors, human intervention and poorly standardized experimental protocols, which can negatively affect the interpretation of the results obtained. In this article, we discuss factors that have a negative impact on the performance of behavioral testing of laboratory animals, modern approaches to overcome them, as well as new technologies, such as visualization of neuronal activity using ion-dependent fluorescent indicators (optogenetics), which expand the boundaries of the study of neuronal networks responsible for behavior by evaluating neuronal function at both the cellular and population levels. Ultimately, this will increase the reliability of the results obtained and provide an opportunity to take a fresh look at the ethological paradigms of a particular transgenic mouse model.

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.

Decreased energy metabolism in the brain correlates with cognitive impairment in Alzheimer’s disease. Accumulating experimental data indicate that lactate transporters and monocarboxylate transporters (MCTs) are directly involved in cerebral energy metabolism. However, to date, changes in lactate levels and MCT content in Alzheimer’s disease remain unclear. The aim of the study was to study the content of lactate and of its transporters – MCT1 and MCT2 in cells of neuronal, astroglial and endothelial nature under acute toxic effects of beta-amyloid (Aβ1–42) in vitro and in vivo. Under conditions of acute toxic action of Aβ1–42 in vivo, a significant (P ≤ 0.05) decrease in the level of lactate in the hippocampal tissue and an increase (P ≤ 0.05) in the dialysate were found. At the same time, a low (P ≤ 0.05) levels of MCT1 and MCT2 was set. In vitro, significantly high (P ≤ 0.05) production of lactate by astrocytes was revealed, coupled with low (P ≤ 0.05) level of MCT2 on neurons. Thus, it was found that Aβ1–42 causes a decrease in the level of lactate in the hippocampal tissue and an increase in its level in dialysate in vivo, which correlates with the impaired level of MCT1 and MCT2. This indicates a violation of energy metabolism due to the acute toxic effect of Aβ1–42. At the same time, the revealed increase in the production of lactate by astrocytes in vitro may indicate the inclusion of a compensatory mechanism aimed at maintaining the astrocyte-neuronal interaction.

Alzheimer’s disease is the most common type of dementia associated with cognitive decline, such as memory and visuospatial skills. Insufficiently effective treatments have prompted the creation of experimental animal models capable of reproducing the pathology of Alzheimer’s disease, especially at the presymptomatic stage, in order to develop and study preventive and therapeutic strategies. To date, none of the developed animal models fully reflects the entire spectrum of neuropathological and cognitive impairments observed in the development of Alzheimer’s disease in humans. However, each model created allows, to one degree or another, to study various aspects of the pathogenesis of the disease, providing an important understanding of the key pathological changes that may occur during its development. In this review, we present a summary of the neuropathological features of Alzheimer’s disease and their relationship to cognitive impairment in the animal models currently in use. We also present in a comparative aspect the features of the development of Alzheimer’s type neurodegeneration using the example of 2 models – genetic and injection, which will make it possible to determine optimal approach when choosing a model for implementing research tasks.