Differential effects of intragastric acid and capsaicin on gastric emptying and afferent input to the rat spinal cord and brainstem

BACKGROUND: Hydrochloric acid (HCl) is a potential threat to the integrity of the gastric mucosa and is known to contribute to upper abdominal pain. We have previously found that gastric mucosal challenge with excess HCl is signalled to the rat brainstem, but not spinal cord, as visualized by expression of c-fos messenger ribonucleic acid (mRNA), a surrogate marker of neuronal excitation. This study examined whether gastric mucosal exposure to capsaicin, a stimulant of nociceptive afferents that does not damage the gastric mucosa, is signalled to both brainstem and spinal cord and whether differences in the afferent signalling of gastric HCl and capsaicin challenge are related to different effects on gastric emptying. RESULTS: Rats were treated intragastrically with vehicle, HCl or capsaicin, activation of neurons in the brainstem and spinal cord was visualized by in situ hybridization autoradiography for c-fos mRNA, and gastric emptying deduced from the retention of intragastrically administered fluid. Relative to vehicle, HCl (0.5 M) and capsaicin (3.2 mM) increased c-fos transcription in the nucleus tractus solitarii by factors of 7.0 and 2.1, respectively. Capsaicin also caused a 5.2-fold rise of c-fos mRNA expression in lamina I of the caudal thoracic spinal cord, although the number of c-fos mRNA-positive cells in this lamina was very small. Thus, on average only 0.13 and 0.68 c-fos mRNA-positive cells were counted in 0.01 mm sections of the unilateral lamina I following intragastric administration of vehicle and capsaicin, respectively. In contrast, intragastric HCl failed to induce c-fos mRNA in the spinal cord. Measurement of gastric fluid retention revealed that HCl suppressed gastric emptying while capsaicin did not. CONCLUSION: The findings of this study show that gastric mucosal exposure to HCl and capsaicin is differentially transmitted to the brainstem and spinal cord. Since only HCl blocks gastric emptying, it is hypothesized that the two stimuli are transduced by different afferent pathways. We infer that HCl is exclusively signalled by gastric vagal afferents whereas capsaicin is processed both by gastric vagal and intestinal spinal afferents

Prolonged Depression-Like Behavior Caused by Immune Challenge: Influence of Mouse Strain and Social Environment

Immune challenge by bacterial lipopolysaccharide (LPS) causes short-term behavioral changes indicative of depression. The present study sought to explore whether LPS is able to induce long-term changes in depression-related behavior and whether such an effect depends on mouse strain and social context. LPS (0.83 mg/kg) or vehicle was administered intraperitoneally to female CD1 and C57BL/6 mice that were housed singly or in groups of 4. Depression-like behavior was assessed with the forced swim test (FST) 1 and 28 days post-treatment. Group-housed CD1 mice exhibited depression-like behavior 1 day post-LPS, an effect that leveled off during the subsequent 28 days, while the behavior of singly housed CD1 mice was little affected. In contrast, singly housed C57BL/6 mice responded to LPS with an increase in depression-like behavior that was maintained for 4 weeks post-treatment and confirmed by the sucrose preference test. Group-housed C57BL/6 mice likewise displayed an increased depression-like behavior 4 weeks post-treatment. The behavioral changes induced by LPS in C57BL/6 mice were associated with a particularly pronounced rise of interleukin-6 in blood plasma within 1 day post-treatment and with changes in the dynamics of the corticosterone response to the FST. The current data demonstrate that immune challenge with LPS is able to induce prolonged depression-like behavior, an effect that depends on genetic background (strain). The discovery of an experimental model of long-term depression-like behavior after acute immune challenge is of relevance to the analysis of the epigenetic and pathophysiologic mechanisms of immune system-related affective disorders

Towards microbiome-informed dietary recommendations for promoting metabolic and mental health: opinion papers of the MyNewGut project

The gut microbiota coexists in partnership with the human host through adaptations to environmental and physiological changes that help maintain dynamic homeostatic healthy states. Break-down of this delicate balance under sustained exposure to stressors (e.g. unhealthy diets) can, however, contribute to the onset of disease. Diet is a key modifiable environmental factor that modulates the gut microbiota and its metabolic capacities that, in turn, could impact human physiology. On this basis, the diet and the gut microbiota could act as synergistic forces that provide resilience against disease or that speed the progress from health to disease states. Associations between unhealthy dietary patterns, non-communicable diseases and intestinal dysbiosis can be explained by this hypothesis. Translational studies showing that dietary-induced alterations in microbial communities recapitulate some of the pathological features of the original host further support this notion. In this introductory paper by the European project MyNewGut, we briefly summarize the investigations conducted to better understand the role of dietary patterns and food components in metabolic and mental health and the specificities of the microbiome-mediating mechanisms. We also discuss how advances in the understanding of the microbiome's role in dietary health effects can help to provide acceptable scientific grounds on which to base dietary advice for promoting healthy living

The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going?

Pain measures traditionally used in rodents record mere reflexes evoked by sensory stimuli; the results thus may not fully reflect the human pain phenotype. Alterations in physical and emotional functioning, pain-depressed behaviors and facial pain expressions were recently proposed as additional pain outcomes to provide a more accurate measure of clinical pain in rodents, and hence to potentially enhance analgesic drug development. We aimed to review how preclinical pain assessment has evolved since the development of the tail flick test in 1941, with a particular focus on a critical analysis of some nonstandard pain outcomes, and a consideration of how sex differences may affect the performance of these pain surrogates. We tracked original research articles in Medline for the following periods: 1973-1977, 1983-1987, 1993-1997, 2003-2007, and 2014-2018. We identified 606 research articles about alternative surrogate pain measures, 473 of which were published between 2014 and 2018. This indicates that preclinical pain assessment is moving toward the use of these measures, which may soon become standard procedures in preclinical pain laboratories.FPU grant from the Spanish Ministry of Education, Culture and SportsSpanish Ministry of Economy and Competitiveness (MINECO, grant SAF2016-80540-R)Ramón Areces FoundationJunta de Andalucía (grant CTS 109)Esteve PharmaceuticalsEuropean Regional Development Fund (ERDF

Räumliche Disparitäten im Bezirk Hartberg-Fürstenfeld

ZusammenfassungZiel dieser vorliegenden Masterarbeit mit dem Titel „Räumliche Disparitäten im Bezirk Hartberg-Fürstenfeld“ ist es, herauszufinden welche ökonomischen und sozioökonomischen Strukturen im Untersuchungsgebiet vorherrschen. Aus der Analyse dieser eben erwähnten Strukturmerkmale soll die Erkenntnis gewonnen werden, ob und in welchem Ausmaß räumliche Disparitäten im Bezirk Hartberg-Fürstenfeld bestehen. Des Weiteren wird der Frage nachgegangen, welche Projekte und Maßnahmen der Regionalentwicklung angewandt wurden und werden, um bestehende Disparitäten zu verringern beziehungsweise abzubauen. Da neben humangeographischen Gesichtspunkten auch die naturräumlichen Gegebenheiten einen großen Einfluss auf das Entstehen und Bestehen von räumlichen Disparitäten ausüben, wird das Untersuchungsgebiet in einem ersten Teil dieser Arbeit hinsichtlich der vorherrschenden physiogeographischen Ausstattung und Charakteristik vorgestellt. Danach erfolgt eine umfangreiche Strukturanalyse, bei der sämtliche Gemeinden des Bezirkes nach ausgewählten Parametern analysiert werden. Die Auswahl dieser Parameter soll ein möglichst breitgefächertes Bild des Bezirkes darlegen, um so schlussendlich die strukturstarken von den strukturschwachen Gemeinden abzugrenzen und bestehende räumliche Disparitäten aufzudecken. Die ausgewählten Strukturmerkmale umfassen die Themen Bevölkerungsstruktur, Wirtschaft sowie öffentliche und soziale Infrastruktur. Für ein besseres räumliches Verständnis der strukturellen Gegebenheiten im Untersuchungsgebiet, werden neben textlichen Erläuterungen zu den einzelnen Parametern auch kartographische Darstellungen und Diagramme präsentiert. Anhand der Ergebnisse der Strukturanalyse wird rasch deutlich, dass die nördlichen, dem Randgebirge zugehörigen Gemeinden, verglichen mit den zentralen und südlichen Gemeinden von Strukturschwäche geprägt sind. Hier sind auch die Passivräume des Bezirkes zu identifizieren. Gründe hierfür sind eine benachteiligte naturräumliche Lage sowie eine schlechte Verkehrsanbindung an das hochrangige Straßennetz und die daraus resultierende schlechtere Erreichbarkeit des Zentralraumes Graz sowie der regionalen Zentren Hartberg und Fürstenfeld. Durch diese Faktoren ist die wirtschaftliche Entwicklung der nördlichen Region im Vergleich zu den zentralen und südlichen Bezirksteilen gehemmt. Als Folge dessen sowie auf Grund von mangelnden Arbeitsplatzangeboten und unzureichender Infrastrukturausstattung, ist eine negative Bevölkerungsentwicklung festzustellen. Wohingegen die Gemeinden um die regionalen Zentren Hartberg und Fürstenfeld als vergleichsweise strukturstark zu bewerten sind. Gründe hierfür sind die gute Verkehrslage, die dadurch verstärkte Ansiedelung von Industrie und hochwertigen Unternehmen, einem guten Angebot an Arbeitsplätzen sowie der vor allem im Thermenland starke Fremdenverkehr.The aim of this master thesis with the title “spatial disparities in the district Hartberg-Fürstenfeld" is to find out what socioeconomic and economic structures prevail in the study area. The analysis of the structural circumstances in the region should gain knowledge about the structures and processes which predominate in the investigation area and also to detect conceivable spatial disparities within the region. Additionally, it should be examined which projects and actions regarding regional development contribute to the reduction of these disparities.In addition to human aspects, the natural environment also has a great influence on the occurrence and existence of spatial disparities. That is why the investigation area is presented in a first part of this thesis with regard to the prevailing physiogeographical and natural features and characteristics. This is followed by an extensive structural analysis, in which all communities in the district are analyzed according to selected parameters. The selection of these parameters is intended to present a holistic picture of the district, in order to isolate the structurally strong communities and to reveal existing spatial disparities. The selected structural features cover the topics of population structure, economy and public and social infrastructure. For a better spatial understanding of the structural conditions in the study area, the textual explanations of the individual parameters are supplemented by cartographic representations and diagrams. On the basis of the results of the structural analysis, it becomes clear that the northern communities, belonging to the bordering mountains, are characterized by structural weaknesses compared with the central and southern municipalities. The reasons for this are a disadvantaged natural environment as well as a poor traffic connection to the high-ranking road network and the resulting poorer accessibility of the central area of Graz and the regional centers Hartberg and Fürstenfeld. These factors hinder the economic development of the northern region compared to the central and southern parts of the district. As a result of this, as well as due to a lack of job offers and inadequate infrastructure, a negative population development has been identified. While the municipalities around the regional centers of Hartberg and Fürstenfeld are comparatively structurally strong. The reasons for this are the good traffic conditions, the intensified settlement of industry and high-quality companies with a relatively good supply of jobs and the strong tourism, especially in the Thermenland.vorgelegt von Alexandra Painsipp, BSc.Abweichender Titel laut Übersetzung des Verfassers/der VerfasserinZusammenfassungen in Deutsch und EnglischKarl-Franzens-Universität Graz, Masterarbeit, 2016(VLID)170074