Over the past decades, the human life span has dramatically increased, and therefore, a steady increase in diseases associated with age (such as Alzheimer’s disease and Parkinson’s disease) is expected. In these neurodegenerative diseases, there is a cognitive decline and memory loss, which accompany increased systemic inflammation, the inflamm-aging, and the insulin resistance. Despite numerous studies of age-related pathologies, data on the contribution of brain insulin resistance and innate immunity components to aging are insufficient. Recently, much research has been focused on the consequences of nutrients and adiposity- and nutrient-related signals in brain aging and cognitive decline. Moreover, given the role of metainflammation in neurodegeneration, lifestyle interventions such as calorie restriction may be an effective way to break the vicious cycle of metainflammation and have a role in social behavior. The various effects of calorie restriction on metainflammation, insulin resistance, and neurodegeneration have been described. Less attention has been paid to the social determinants of aging and the possible mechanism by which calorie restriction might influence social behavior. The purpose of this review is to discuss current knowledge in the interdisciplinary field of geroscience—immunosenescence, inflamm-aging, and metainflammation—which makes a significant contribution to aging. A substantial part of the review is devoted to frontiers in the brain insulin resistance in relation to neuroinflammation. In addition, we summarize new data on potential mechanisms of calorie restriction that influence as a lifestyle intervention on the social brain. This knowledge can be used to initiate successful aging and slow the onset of neurodegenerative diseases.

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Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. In recent years, attention of researchers has increasingly been focused on studying the role of brain insulin resistance (BIR) in the AD pathogenesis. Neuroinflammation makes a significant contribution to the BIR due to the activation of NLRP3 inflammasome. This study was devoted to the understanding of the potential therapeutic roles of the NLRP3 inflammasome in neurodegeneration occurring concomitant with BIR and its contribution to the progression of emotional disorders. Methods: To test the impact of innate immune signaling on the changes induced by Aβ1-42 injection, we analyzed animals carrying a genetic deletion of the Nlrp3 gene. Thus, we studied the role of NLRP3 inflammasomes in health and neurodegeneration in maintaining brain insulin signaling using behavioral, electrophysiological approaches, immunohistochemistry, ELISA and real-time PCR. Results: We revealed that NLRP3 inflammasomes are required for insulin-dependent glucose transport in the brain and memory consolidation. Conclusions NLRP3 knockout protects mice against the development of BIR: Taken together, our data reveal the protective role of Nlrp3 deletion in the regulation of fear memory and the development of Aβ-induced insulin resistance, providing a novel target for the clinical treatment of this disorder.

Alzheimer's disease is characterized by the loss of neurons, the accumulation of intracellular neurofibrillary tangles and extracellular amyloid plaques in the brain. However, there are contradicting data on differences in neurogenesis at the onset of the disease or before the formation of amyloid plaques. As awareness of the importance of the pre-symptom phase in neurodegenerative diseases grows in the context of early diagnosis and pathogenesis, we analyzed the critical periods of adult hippocampal neurogenesis at an early stage under the action of soluble Ab1-42 beta-amyloid. The proliferation, migration and neuronal cells survival were evaluated in mice with an injection of soluble amyloid beta-oligomers. It was found that the injection of Ab1-42 oligomers causes a decrease in cell proliferation in the mouse hippocampus. Despite the preservation of the neuroblast pool in animals after beta-amyloid injection, the process of radial migration is disrupted, and an increase in apoptosis in the neurogenic niche was revealed. Thus, our results demonstrate damage of neurogenesis critical stages: the progenitor cells, neuroblast migration, the integration of immature neurons, and the survival of neurons under application of soluble beta-amyloid oligomers. The obtained data indicate decline in proliferation rate in the subgranular zone, that is accompanied by ectopic differentiation and disturbed migration, producing, apparently, abnormal neurons that have lower survival rates. That could lead to a decrease in mature neurons numbers and the number of cells in the granular layer of the dentate gyrus.

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Особенности пролиферации и миграции клеток головного мозга при когнитивном тренинге животных Комлева Ю.К., Горина Я.В., Черных А.И. и др.