Chronic fluoxetine administration enhances synaptic plasticity and increases functional dynamics in hippocampal CA3-CA1 synapses

Recent studies demonstrate that chronic administration of the widely used antidepressant fluoxetine (FLX) promotes neurogenesis, synaptogenesis and synaptic plasticity in the adult hippocampus, cortex and amygdala. However, the mechanisms underlying these effects and how are they related to the clinical antidepressant efficacy are still poorly understood. We show here that chronic FLX administration decreases hippocampus-associated neophobia in naive mice. In parallel, electrophysiological recordings in hippocampal CA3-CA1 circuitry revealed that the FLX treatment resulted in increased short and long-term plasticity likely attributed to changes in presynaptic function. These changes were accompanied by enhancement in the expression of proteins related to vesicular trafficking and release, namely synaptophysin, synaptotagmin 1, MUNC 18 and syntaxin 1. Thus, chronic FLX administration is associated with enhanced synaptic dynamics atypical of mature CA1 synapses, elevated hippocampal plasticity, improved hippocampus-dependent behavior as well as altered expression of synaptic proteins regulating neurotransmitter trafficking and release. The results support the idea that antidepressants can promote neuronal plasticity and show that they can increase the functional dynamic range and information processing in synaptic circuitries. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

Neurophysiological mechanisms of plasticity induced in adult brain

Dynamic modifications of synaptic connectivity enables the brain to adequately respond to environmental challenges. This ability, known as synaptic plasticity, peaks during the early postnatal period, yet it is maintained throughout life. Interestingly, antidepressants (ADs) and AD-like drugs can promote neuronal plasticity in the adult brain, a phenomenon recently suggested to contribute to the mood-improving effects of ADs. However, the mechanisms underlying AD-induced neuronal network refinement are still poorly understood. The main goal of this thesis was to advance our understanding of the mechanisms associated with pharmacologically-enhanced plasticity in the adult brain. Two pharmacologically distinct compounds with AD-like actions, namely the selective serotonin reuptake inhibitor fluoxetine (Flx) and the volatile anesthetic isoflurane were used to enhance synaptic plasticity in the rodent cortex and hippocampus. After drug exposure, behavioral, molecular, histological and in vitro electrophysiological approaches were utilized to investigate the effects of Flx and ISO on synaptic function and plasticity. Using electrophysiological recordings in brain slices, we show that chronic Flx treatment results in increased short- and long-term plasticity as well as enhanced basal transmission in excitatory CA3-CA1 synapses in the hippocampus. These changes were paralleled by an activity-dependent enhancement in the expression of proteins related to vesicular trafficking and release, such as synaptophysin, synaptotagmin 1, mammalian uncoordinated protein 18 (Munc 18) and syntaxin 1. Moreover, Flx treatment reduced the percentage of parvalbumin-expressing GABAergic neurons, increased the expression of polysialylated-neural cell adhesion molecule (PSA-NCAM) and decreased the expression of the potassium-chloride co-transporter 2 (KCC2) in the basolateral amygdala and in the medial prefrontal cortex (mPFC). All the above findings are likely to be attributed to increased dynamic range of synaptic plasticity induced by Flx. Our behavioral findings demonstrate that long term Flx administration in combination with extinction training results in long-term loss of fearful memories while the Flx treatment alone failed to influence fear behavior. These data suggest that behavioral training is indispensable for the guidance of Flx-induced network plasticity. Exposure to isoflurane promotes long-term synaptic plasticity and enhances basal synaptic transmission in excitatory CA3-CA1 synapses in the mouse hippocampus. These changes were correlated with increased tropomyosin receptor kinase B (TrkB) signaling through the mammalian target of rapamycin (mTOR) pathway in the prefrontal cortex and hippocampus and led to rapid antidepressant-like behavioral effects in the forced swim test. Taken together, our findings highlight that Flx and isoflurane enhance synaptic plasticity in hippocampal and cortical excitatory synapses, however, the underlying molecular mechanisms as well as behavior improvements were different. In conclusion, the results described in this work provide a mechanistic background for adult brain plasticity and network tuning, with high practical significance to the design of clinical therapy

Combination of fluoxetine and extinction treatments forms a unique synaptic protein profile that correlates with long-term fear reduction in adult mice

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Innovative Development of Higher Education

The article considers the essence of innovation in higher education and the integration of educational, scientific and industrial scope. Disclosed forms of innovation in higher education, as well as their role in the interaction of education, science and business. Defined forms of cooperation between education, science and business. Review the modalities of cooperation between education and business in the examples of financial and technological academy city of Korolev, Moscow region. Were revealed directions of innovation developing higher education.And also drawn conclusions on the matter. DOI: 10.5901/mjss.2015.v6n4p59

Derivation, Characterization, and Stable Transfection of Induced Pluripotent Stem Cells from Fischer344 Rats

The rat represents an important animal model that, in many respects, is superior to the mouse for dissecting behavioral, cardiovascular and other physiological pathologies relevant to humans. Derivation of induced pluripotent stem cells from rats (riPS) opens the opportunity for gene targeting in specific rat strains, as well as for the development of new protocols for the treatment of different degenerative diseases. Here, we report an improved lentivirus-based hit-and-run riPS derivation protocol that makes use of small inhibitors of MEK and GSK3. We demonstrate that the excision of proviruses does not affect either the karyotype or the differentiation ability of these cells. We show that the established riPS cells are readily amenable to genetic manipulations such as stable electroporation. Finally, we propose a genetic tool for an improvement of riPS cell quality in culture. These data may prompt iPS cell-based gene targeting in rat as well as the development of iPS cell-based therapies using disease models established in this species

Опис до патенту на корисну модель № 70696 "Пристрій захисту групи асинхронних електродвигунів від аварійних режимів роботи"

Пристрій захисту групи асинхронних електродвигунів від аварійних режимів роботи містить мікроконтролер, канал зв'язку "прийом - передача", блок вводу даних контролю, блок цифрової індикації, блок живлення, блок аварійної звукової сигналізації, блок діагностування та захисту електродвигуна, який містить блок вимірювання та контролю фазних струмів, блок вимірювання температури статорної обмотки, блок контролю неповнофазного режиму, блок живлення, мікропроцесорний блок обробки інформації, канал зв'язку "прийом - передача", виконавчий блок, комунікаційний блок. Блок діагностування та захисту електродвигуна містить блок контролю вологості в корпусі електродвигун

TrkB overexpression in mice buffers against memory deficits and depression-like behavior but not all anxiety- and stress-related symptoms induced by developmental exposure to methylmercury

Peer reviewe

Isoflurane produces antidepressant effects and induces TrkB signaling in rodents

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3 beta (GSK3 beta). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.Peer reviewe

Роль навчальної дисципліни «Електроніка та мікросхемотехніка» у формуванні професійних компетенцій майбутнього фахівця аграрної сфери

UK: У роботі досліджено роль, форми та методи викладання дисципліни «Електроніка та мікросхемотехніка» в Таврійському державному агротехнологічному університеті (ТДАТУ) для вдосконалення професійної підготовки майбутніх фахівців аграрної сфери. EN: The work is devoted to role, forms and methods of teaching the discipline «Electronics and microcircuitry» at the Tavria State agrotechnological university (TSATU) for improving the training of future specialists in the agrarian sector