Натрийуретические пептиды (НУП) являются важными биомаркерами в диагностике и определении прогноза у пациентов с сердечной недостаточностью (СН). Оценка динамики концентрации НУП (BNP, Nt -proBNP) может быть использована в качестве критерия успешности проводимой терапии. так, при достижении целевых уровней НУП можно прогнозировать благоприятный исход заболевания. В настоящее время лечение СН с учетом уровней НУП является частью рекомендаций по лечению СН (класс IIа) и улучшению ее исхода (класс IIб) в США, однако такой подход не используется в российских клиниках. Цель. Представить современный взгляд на возможность использования НУП для оценки эффективности проводимой терапии пациентов с СН. Ключевые слова: натрийуретические пептиды, сердечная недостаточность, оценка эффективности терапии.

Федеральное государственное бюджетное учреждение «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний» Сибирского отделения Российской академии медицинских наук, Кемерово, Россия

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Development of anxiety- and depression-like states under chronic social defeat stress in mice has been shown by many experimental studies. In this article, the differentially expressed Slc25* family genes encoding mitochondrial carrier proteins were analyzed in the brain of depressive (defeated) mice versus aggressive mice winning in everyday social confrontations. The collected samples of brain regions were sequenced at JSC Genoanalytica (
 http://genoanalytica.ru/
 , Moscow, Russia). Changes in the expression of the 20 Slc25* genes in the male mice were brain region- and social experience (positive or negative)-specific. In particular, most Slc25* genes were up-regulated in the hypothalamus of defeated and aggressive mice and in the hippocampus of defeated mice. In the striatum of defeated mice and in the ventral tegmental area of aggressive mice expression of mitochondrial transporter genes changed specifically. Significant correlations between expression of most Slc25* genes and mitochondrial Mrps and Mrpl genes were found in the brain regions. Altered expression of the Slc25* genes may serve as a marker of mitochondrial dysfunction in brain, which accompanies the development of many neurological and psychoemotional disorders.

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Altered Slc25 family gene expression as markers of mitochondrial dysfunction in brain regions under experimental mixed anxiety/depression-like disorder.

Modes of division and differentiation of neural stem cells.

Throughout adulthood, the dentate gyrus continues to produce new granule cells, which integrate into the hippocampal circuitry. New neurons have been linked to several known functions of the hippocampus, including learning and memory, anxiety and stress regulation, and social behavior. We explored whether transgenic reduction of adult-born neurons in mice would impair social memory and the formation of social dominance hierarchies. We used a conditional transgenic mouse strain [thymidine kinase (TK) mice] that selectively reduces adult neurogenesis by treatment with the antiviral drug valganciclovir (VGCV). TK mice treated with VGCV were unable to recognize conspecifics as familiar 24 h after initial exposure. We then explored whether reducing new neurons completely impaired their ability to acquire or retrieve a social memory and found that TK mice treated with VGCV were able to perform at control levels when the time between exposure (acquisition) and reexposure (retrieval) was brief. We next explored whether adult-born neurons are involved in dominance hierarchy formation by analyzing their home cage behavior as well as their performance in the tube test, a social hierarchy test, and did not find any consistent alterations in behavior between control and TK mice treated with VGCV. These data suggest that adult neurogenesis is essential for social memory maintenance, but not for acquisition nor retrieval over a short time frame, with no effect on social dominance hierarchy. Future work is needed to explore whether the influence of new neurons on social memory is mediated through connections with the CA2, an area involved in social recognition.

Adult-Born Neurons in the Hippocampus Are Essential for Social Memory Maintenance.

Repeated experience of winning in a social conflict setting elevates levels of aggression and may lead to violent behavioral patterns. Here, we use a paradigm of repeated aggression and fighting deprivation to examine changes in behavior, neurogenesis, and neuronal activity in mice with positive fighting experience. We show that for males, repeated positive fighting experience induces persistent demonstration of aggression and stereotypic behaviors in daily agonistic interactions, enhances aggressive motivation, and elevates levels of anxiety. When winning males are deprived of opportunities to engage in further fights, they demonstrate increased levels of aggressiveness. Positive fighting experience results in increased levels of progenitor cell proliferation and production of young neurons in the hippocampus. This increase is not diminished after a fighting deprivation period. Furthermore, repeated winning experience decreases the number of activated (c-fos-positive) cells in the basolateral amygdala and increases the number of activated cells in the hippocampus; a subsequent no-fight period restores the number of c-fos-positive cells. Our results indicate that extended positive fighting experience in a social conflict heightens aggression, increases proliferation of neuronal progenitors and production of young neurons in the hippocampus, and decreases neuronal activity in the amygdala; these changes can be modified by depriving the winners of the opportunity for further fights.

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Irina N. Kovalenko

Papers

Altered Hippocampal Neurogenesis and Amygdalar Neuronal Activity in Adult Mice with Repeated Experience of Aggression