Репозиторий Университета

© Springer Science+Business Media New York 2016. A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

© 2018 Bentham Science Publishers. A number of biological and clinical characteristics typical of late life depression (LLD) have been suggested by recent research findings. The close association of LLD with cognitive impairment is now well documented and evidenced. However, it is still not clear whether it is depression that leads to cognitive decline, and in more severe cases, to dementia. The work presented in this review article suggests that depression and dementia frequently and strongly copresent, even if the causality remains largely opaque.

В области изучения нейробиологии униполярных депрессивных расстройств (УДР) перспективными считаются нейровизуализационные методы, особенно позитронно-эмиссионная томография (ПЭТ) и функциональная магнитно-резонансная томография (фМРТ). В статье приводится обзор современных нейровизуализационных данных, касающихся структурно-функциональных особенностей головного мозга у лиц, страдающих УДР. Результаты отдельных исследований представлены в зависимости от особенностей методов их проведения (состояние покоя, выполнение когнитивных и эмоциональных тестов) и соотнесены с основными нейробиологическими концепциями развития депрессивных расстройств. Отдельно рассмотрены возможности нейровизуализационных исследований для оценки и прогнозирования результатов антидепрессивной терапии.

Цель исследования. Изучение связи между генами иммунной системы и депрессией, а также ее эндофенотипами (невротизм и личностная тревожность) при ишемической болезни сердца (ИБС). Материал и методы. Исследование проведено в группе мужчин с ИБС с депрессией (78 человек) и без нее (91 человек), а также у здоровых добровольцев мужского пола (127 человек). Изучены полиморфизмы генов интерлейкина-4 (IL-4 –589C/T), интерлейкина-6 (IL-6 –174G/C), фактора некроза опухолей-α (TNF-α –308G/A) и С-реактивного белка (CRP –717A/G). Результаты. Обнаружена ассоциация полиморфизма IL-6 –174 G/C с депрессией, коморбидной ИБС (р=0,01; ОШ=2,3 ДИ 95% 1,2—4,3), которая выражалась в повышении частоты высокоэкспрессивного аллеля G в группе больных с депрессией. Полиморфизм IL-4 –589C/T был ассоциирован с ИБС: частота генотипа СС IL-4 –589C/T была выше в группе больных по сравнению с контрольной группой независимо от наличия депрессии (р=0,007; ОШ=2,1 ДИ 95% 1,2—3,4). Полиморфизмы TNF-α –308G/A и CRP –717A/G не были ассоциированы с депрессией при ИБС. Значимых различий в выраженности невротизма и личностной тревожности у носителей различных генотипов по локусам IL-4 –589 C/T, IL-6 –174 G/C, TNF-α –308 G/A, CRP –717A/G выявлено не было. Заключение. Ассоциация полиморфизма IL-6 –174G/C с депрессией, коморбидной ИБС, согласуется с данными литературы о роли IL-6 в развитии депрессии у кардиологических больных.

Background: The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown that environmental enrichment and exercise, two non-pharmacological interventions that are beneficial decreasing the progression of Alzheimer disease (AD) and depressive-like behavior, enhance hippocampal VEGF expression and neurogenesis. Furthermore, the stimulation of VEGF expression promotes neurotransmission and synaptic plasticity processes such as neurogenesis. It is thought that these VEGF actions in the brain, may underly its beneficial therapeutic effects against psychiatric and other neurological conditions.

Conclusion: In this review, evidence linking VEGF deficit with the development of AD as well as the potential role of VEGF signaling as a therapeutic target for cotinine and other interventions in neurodegenerative conditions are discussed.

A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

В области изучения нейробиологии униполярных депрессивных расстройств (УДР) перспективными считаются нейровизуализационные методы, особенно позитронно-эмиссионная томография (ПЭТ) и функциональная магнитно-резонансная томография (фМРТ). В статье приводится обзор современных нейровизуализационных данных, касающихся структурно-функциональных особенностей головного мозга у лиц, страдающих УДР. Результаты отдельных исследований представлены в зависимости от особенностей методов их проведения (состояние покоя, выполнение когнитивных и эмоциональных тестов) и соотнесены с основными нейробиологическими концепциями развития депрессивных расстройств. Отдельно рассмотрены возможности нейровизуализационных исследований для оценки и прогнозирования результатов антидепрессивной терапии.

Цель исследования. Изучение связи между генами иммунной системы и депрессией, а также ее эндофенотипами (невротизм и личностная тревожность) при ишемической болезни сердца (ИБС). Материал и методы. Исследование проведено в группе мужчин с ИБС с депрессией (78 человек) и без нее (91 человек), а также у здоровых добровольцев мужского пола (127 человек). Изучены полиморфизмы генов интерлейкина-4 (IL-4 –589C/T), интерлейкина-6 (IL-6 –174G/C), фактора некроза опухолей-α (TNF-α –308G/A) и С-реактивного белка (CRP –717A/G). Результаты. Обнаружена ассоциация полиморфизма IL-6 –174 G/C с депрессией, коморбидной ИБС (р=0,01; ОШ=2,3 ДИ 95% 1,2—4,3), которая выражалась в повышении частоты высокоэкспрессивного аллеля G в группе больных с депрессией. Полиморфизм IL-4 –589C/T был ассоциирован с ИБС: частота генотипа СС IL-4 –589C/T была выше в группе больных по сравнению с контрольной группой независимо от наличия депрессии (р=0,007; ОШ=2,1 ДИ 95% 1,2—3,4). Полиморфизмы TNF-α –308G/A и CRP –717A/G не были ассоциированы с депрессией при ИБС. Значимых различий в выраженности невротизма и личностной тревожности у носителей различных генотипов по локусам IL-4 –589 C/T, IL-6 –174 G/C, TNF-α –308 G/A, CRP –717A/G выявлено не было. Заключение. Ассоциация полиморфизма IL-6 –174G/C с депрессией, коморбидной ИБС, согласуется с данными литературы о роли IL-6 в развитии депрессии у кардиологических больных.

Background: The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown that environmental enrichment and exercise, two non-pharmacological interventions that are beneficial decreasing the progression of Alzheimer disease (AD) and depressive-like behavior, enhance hippocampal VEGF expression and neurogenesis. Furthermore, the stimulation of VEGF expression promotes neurotransmission and synaptic plasticity processes such as neurogenesis. It is thought that these VEGF actions in the brain, may underly its beneficial therapeutic effects against psychiatric and other neurological conditions.

Conclusion: In this review, evidence linking VEGF deficit with the development of AD as well as the potential role of VEGF signaling as a therapeutic target for cotinine and other interventions in neurodegenerative conditions are discussed.