Storage of neural histamine and histaminergic neurotransmission is VMAT2 dependent in the zebrafish

Monoaminergic neurotransmission is greatly dependent on the function of the vesicular monoamine transporter VMAT2, which is responsible for loading monoamines into secretory vesicles. The role of VMAT2 in histaminergic neurotransmission is poorly understood. We studied the structure and function of the histaminergic system in larval zebrafish following inhibition of VMAT2 function by reserpine. We found that reserpine treatment greatly reduced histamine immunoreactivity in neurons and an almost total disappearance of histamine-containing nerve fibers in the dorsal telencephalon and habenula, the most densely innervated targets of the hypothalamic histamine neurons. The reserpine treated larvae had an impaired histamine-dependent dark-induced flash response seen during the first second after onset of darkness, implying that function of the histaminergic network is VMAT2 dependent. Levels of histamine and other monoamines were decreased in reserpine treated animals. This study provides conclusive evidence of the relevance of VMAT2 in histaminergic neurotransmission, further implying that the storage and release mechanism of neural histamine is comparable to that of other monoamines. Our results also reveal potential new insights about the roles of monoaminergic neurotransmitters in the regulation of locomotion increase during adaptation to darkness.Peer reviewe

EXIT: An alternative approach for structural cross-impact modeling and analysis

Cross-impact methods are planning, foresight and decision support tools often used in conjunction with the scenario technique. They enable systems modeling in a theory-driven way, grounded in expert judgment and understanding. This article presents the EXIT approach, a novel modeling technique and a computational method for structural cross-impact analysis. EXIT extracts insights from an expert-sourced cross-impact model, which describes the structure of direct interactions within a system. The EXIT transformation produces a relative quantification of the emergent, systemic relationships between model components, effectuating over the complex web of interactions in the system. Compared to the more established matrix multiplication approach, EXIT produces novel and more detailed analytical outputs on the basis of similar input, and offers new analytical possibilities in structural cross-impact analysis. A software implementing the EXIT transformation is freely available.</p

Finnish neuroscience from past to present

Non peer reviewe

Inhibition of Homophilic Interactions and Ligand Binding of the Receptor for Advanced Glycation End Products by Heparin and Heparin-Related Carbohydrate Structures

Background: Heparin and heparin-related sulphated carbohydrates inhibit ligand binding of the receptor for advanced glycation end products (RAGE). Here, we have studied the ability of heparin to inhibit homophilic interactions of RAGE in living cells and studied how heparin related structures interfere with RAGE–ligand interactions. Methods: Homophilic interactions of RAGE were studied with bead aggregation and living cell protein-fragment complementation assays. Ligand binding was analyzed with microwell binding and chromatographic assays. Cell surface advanced glycation end product binding to RAGE was studied using PC3 cell adhesion assay. Results: Homophilic binding of RAGE was mediated by V1- and modulated by C2-domain in bead aggregation assay. Dimerisation of RAGE on the living cell surface was inhibited by heparin. Sulphated K5 carbohydrate fragments inhibited RAGE binding to amyloid β-peptide and HMGB1. The inhibition was dependent on the level of sulfation and the length of the carbohydrate backbone. α-d-Glucopyranosiduronic acid (glycyrrhizin) inhibited RAGE binding to advanced glycation end products in PC3 cell adhesion and protein binding assays. Further, glycyrrhizin inhibited HMGB1 and HMGB1 A-box binding to heparin. Conclusions: Our results show that K5 polysaccharides and glycyrrhizin are promising candidates for RAGE targeting drug development.Peer reviewe

Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation.

Amphoterin is a protein enhancing process extension and migration in embryonic neurons and in tumor cells through binding to receptor for advanced glycation end products (RAGE), a multiligand transmembrane receptor. S100 proteins, especially S100B, are abundantly expressed in the nervous system and are suggested to function as cytokines with both neurotrophic and neurotoxic effects. However, the cell surface receptor for the cytokine function of S100B has not been identified. Here we show that two S100 family proteins, S100B and S100A1, activate RAGE in concert with amphoterin inducing neurite outgrowth and activation of transcription factor NF-kappaB. Furthermore, activation of RAGE by amphoterin and S100B promotes cell survival through increased expression of the anti-apoptotic protein Bcl-2. However, whereas nanomolar concentrations of S100B induce trophic effects in RAGE-expressing cells, micromolar concentrations of S100B induce apoptosis in an oxidant-dependent manner. Both trophic and toxic effects are specific for cells expressing full-length RAGE since cells expressing a cytoplasmic domain deletion mutant of RAGE are unresponsive to these stimuli. These findings suggest that activation of RAGE by multiple ligands is able to promote trophic effects whereas hyperactivation of RAGE signaling pathways promotes apoptosis. We suggest that RAGE is a signal-transducing receptor for both trophic and toxic effects of S100B

Electromechanical film sensor device for dynamic force recordings from canine limbs

An equipment based on the electromechanical film (EMF) sensors was designed for the measurementof forces acting upon canine limbs. EMF forms an elastic electret, which generates on its surface an electric charge proportional to the the force applied on it. The EMF sensors were calibrated using a conventional material testing device with cyclic loads. The beagles were trained on a treadmill working at horizontal position or with either 15° uphill or downhill inclination. The treadmill belt speed varied from 2.5 km/h to 7.5 km/h. The force under the canine paws varied depending on the inclination of the treadmill. When the dogs ran uphill, weight-bearing on hind1imbs increased 11% but the weight-bearing 0n forelimbs did not change. Downhill running increased weight-bearing on forelimbs by 8% and decreased weight-bcaring of the hindlimbs by 5%. Immobilization of the right hind] imb increased weightbearing on both forelimbs by 7-25% and on the left hindlimb by 56%. One month after a 30° valgus osteotomy operation at the right tibia, the dynamic force recorded From the operated hindlimb was 69% of the control value. Three months after osteotomy, the weight-bearing of the operated limb approachednormal situation. Our results suggest that the EMF sensor is a reliable method for the measurement of dynamic forces acting on the weight-bearing limbs of the dogs

Green economic development in Lao PDR : a Sustainability Window analysis of Green Growth Productivity and the Efficiency Gap

A novel 'Sustainability Window' (SuWi) approach is applied for simultaneous analysis of the pillars of sustainable development; social, environmental and economic, of Lao PDR. This new method employs a variety of indicators for a comprehensive and holistic analysis of sustainable development and green inclusive economy. The analysis is grounded in the assumption that economic development is required for social development, but that simultaneously development needs to be guarded or limited to protect the environment that underpins it. As all three dimensions of sustainable development are interlinked, a comprehensive analysis requires an analytical approach that is simultaneous. The analyses provide information on minimum levels of economic development that are needed to fulfil social sustainability criteria, in tandem with the maximum economic development that avoids breaching environmental sustainability criteria. If actual economic growth lies between these minima and maxima, we can interpret that development is more sustainable with respect to the relationships embodied by the selected social and environmental indicators. The main source of data is the database of the Sustainable Society Index (SSI) developed by the Sustainable Society Foundation (SSF). The indicators used by SSI have been chosen for the Sustainability Window analysis as they can be used to assess both 'weak' and 'strong' interpretations of sustainability. Weak sustainability is defined operationally as no increase in the environmental or carbon emissions intensity of the economy, while strong sustainability is defined as no increase in absolute emissions. Further, a novel Environmental Efficiency Gap analysis has been included in the Sustainability Window. This provides information about the necessary improvement in GDP production efficiency with respect to environmental emissions. Sustainability Window combined with Environmental Efficiency Gap analysis, provides critical knowledge for planners and decision makers. It provides strategic indications of how to aim for social and environmental sustainability through economic investment and growth targets. These new methods can be used in transdisciplinary research of sustainable development and can also assist in national and regional comparisons. In the case of Lao PDR, the analysis needs to be broadened for more fundamental understanding of the gaps and weaknesses. SuWi can be used to assess the sustainable development needed to address the Sustainable Development Goals by 2030. The SuWi does not provide direct policy recommendations as such, but helps to inform decision makers about the direction of development pathways towards these key goals. (C) 2018 The Authors. Published by Elsevier Ltd.Peer reviewe

Oxidative Stress and Regulation of Pink1 in Zebrafish (Danio rerio)

Peer reviewe

Short photoperiod-induced decrease of histamine H3 receptors facilitates activation of hypothalamic neurons in the Siberian Hamster

Nonhibernating seasonal mammals have adapted to temporal changes in food availability through behavioral and physiological mechanisms to store food and energy during times of predictable plenty and conserve energy during predicted shortage. Little is known, however, of the hypothalamic neuronal events that lead to a change in behavior or physiology. Here we show for the first time that a shift from long summer-like to short inter-like photoperiod, which induces physiological adaptation to winter in the Siberian hamster, including a body weight decrease of up to 30%, increases neuronal activity in the dorsomedial region of the arcuate nucleus (dmpARC) assessed by electro physiological patch-clamping recording. Increased neuronal activity in short days is dependent on a photoperiod-driven down-regulation of H3 receptor expression and can be mimicked in long-day dmpARC neurons by the application of the H3 receptor antagonist, clobenproprit. Short-day activation of dmpARC neurons results in increased c-Fos expression. Tract tracing with the trans-synaptic retrograde tracer, pseudorabies virus, delivered into adipose tissue reveals a multisynaptic neuronal sympathetic outflow from dmpARC to white adipose tissue. These data strongly suggest that increased activity of dmpARC neurons, as a consequence of down-regulation of the histamine H3 receptor, contributes to the physiological adaptation of body weight regulation in seasonal photoperiod