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Browsing by study line "Cell och systems fysiologi"

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  • Nykänen, Roope (2023)
    Diets of wild owls have been studied by pellets, when the nutritional value of owl prey remains unclear. Fatty acids are an essential part of animal nutrition, acting as energy reserve, building blocks of membranes and precursors for signaling molecules. I studied whether Finnish owl species have species-specific characteristics in the fatty acid profiles of adipose tissue due to different diets and feeding habits. I also compared fatty acid profiles between wild and captive owls to elucidate if the diet of captive owls resembles the diet in the wild. Fatty acids from visceral adipose tissue and a liver were transesterified to fatty acid methyl esters, which were identified and quantified by gas-chromatographs linked to either a mass spectrometry or flame ionisation detector. The fatty acid compositions were compared with Principal Component Analysis and statistical significance of the separations between species, origins and tissues were studied by Soft Independent Modelling of Class Analogies. Differences in the relative concentrations of individual fatty acids and their structural category sums were evaluated by the Kruskal-Wallis test followed by the Wilcoxon rank-sum test. Compared to wild owls, captive owl (snowy owl Bubo scandiacus and Eurasian eagle-owl Bubo bubo) adipose tissues had lower relative concentrations of many long-chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. The captive owls also had lower n-3 PUFA/n-6 PUFA ratio than the wild owls. I suggest that these differences arise from anthropogenic food given to the prey of the captive owls. In the future, the feeding and breeding of captive owls could be improved and potential health hazards prevented by giving the owls a diet rich in long-chain PUFAs, either by giving the prey more versatile diet or adding supplements to the owl’s diet. The adipose tissues of wild Eurasian eagle-owls contained higher total relative concentrations of monounsaturated fatty acids than the species belonging to the Strix genus. On the other hand, long-chain PUFAs were more prominent in the Strix owls. I suggest that these differences in the fatty acid composition are due to the disparities in feeding behaviour: the Eurasian eagle-owls eat carrions and large prey that cannot be swallowed whole, which may lead to consuming more the body outer parts of the prey. The fatty acid composition of the eagle-owls can also be affected by urban prey that have consumed anthropogenic food. In the future, the fatty acid composition of wild prey should be examined to be able to evaluate the prey composition of owls and its effect on the owl fatty acid profile with physiological consequences, the knowledge that could be used in the future decision-making that supports the conservation of owls.
  • Lindberg, Maiju (2023)
    As the most common mental disorder, anxiety disorders present a major burden to healthcare worldwide and a challenging problem to overcome for the ones suffering from it. Recently, researchers have started to recognize that the relationship between sleep and anxiety disorders is bidirectional; disturbed sleep is a potential risk factor for the progression of anxiety and anxiety can lead to sleep disturbances. However, the neural mechanisms underlying anxiety and sleep problems are still poorly recognized. In this study, we used a chronic sleep fragmentation (SF) paradigm to investigate how disturbed sleep alters anxiety-like behavior in mice and what are the potential underlying neuronal mechanisms. This model was chosen because we wanted to focus on a common form of disturbed sleep in humans rather than total sleep deprivation. We measured anxiety-like behavior in the light-dark box and open field tests right after the 2-week SF period and again after a week of recovery. Additionally, we performed immunohistochemical analysis to study prolonged cell activity (transcription factor ∆FosB), parvalbumin (PV) interneurons and perineuronal net (PNN) structures in the medial prefrontal cortex (mPFC) of the mice. Changes in mPFC activity and related brain areas are associated to anxiety in humans and anxiety-like behavior in rodents alike. Similarly, changes in PV interneurons and PNNs, that regulates PV cell function, are associated to anxiety-like behavior. However, PV interneurons and PNNs have not been previously studied in a setting that combines sleep fragmentation and anxiety-like behavior. We found that chronic SF increases anxiety-like behavior in female mice and that this effect persists at least for a week. Conversely, we did not observe significant increase in anxiety-like behavior in male mice. Both female and male mice showed decrease in ∆FosB in the mPFC suggesting that SF treated mice had lower overall levels of cell activity. Similarly, we found that SF treated mice had decreased PV interneuron intensity in both sexes which could indicate changes in the cell activity. However, the pattern of changes in the IHC results was not identical in males and females. Based on the IHC results, we suggest that SF affects neuronal processes in both sexes but the disparity in them could explain the difference in the behavioral effect. This thesis shows that disturbed sleep can lead to increased anxiety-like behavior in rodent models and recognizes potential targets to study the mechanisms behind the phenomena.
  • Lackman, Madeleine Helena (2022)
    Diabetes mellitus is an incurable disease caused by dysfunctional insulin signaling. The brown adipose tissue (BAT) serves as a hotspot for both lipid and glucose consumption and is thus an attractive target for treating metabolic diseases. Newly surfacing evidence suggest that the endothelial cells (ECs) lining the inner layer of vessels might regulate the morphology and function of adipose tissues. Several studies, including our own, suggest that the vessel density is negatively affected by metabolic diseases. As the BAT is an important organ for systemic lipid and glucose metabolism, and as the effects of metabolic diseases on BAT vessels are not adequately explored, I wanted to investigate how the BAT vasculature changes upon early time points of type 1 (T1D) and 2 (T2D) diabetes in this thesis work. To this end, I used mouse models with chemically induced T1D and genetic T2D and characterized these models with immunohistochemical analyses and immunoassays. To explore the transcriptomic landscapes of ECs and adipose stem cells (ASCs), I analyzed scRNAseq data of BAT stromal vascular fractions (SVF), focusing on changes in gene expression and EC-ASC interactions at a transcriptomic level. Also, by using a publicly available single-cell RNA sequencing (scRNAseq) dataset, I compared BAT SVF gene expression to complement the data resulting from our experiments. The results from this work reveal differential angiogenic responses in the T1D and T2D mouse models and open new avenues of research into how these different pathways are activated and how we can take advantage of these differences to treat diseases. All in all, this work will support the efforts in developing better options for future diabetes prevention, diagnosis, and care.
  • Lalli, Marianne (2024)
    Background: The infant gut microbiome undergoes major temporal changes in the first year of life, crucial for supporting normal development and long-term health. The immense diversity of fiber structures in breast milk and later in solid foods pose unique selection pressures on the gut microbiome maturation by providing novel substrates for the microbiota. However, the longitudinal impact of complementary food-derived fibers on the taxonomic and functional maturation of the gut microbiome during the gradual transition from breast milk to solid foods is not well understood. Objectives: My objective was to examine how breast milk, its fiber and complementary food fibers in the broader context of overall infant diet may affect the gut microbiome bacterial species composition and support age-appropriate gut bacterial maturation trajectories during first year of life. Methods: Longitudinal and cross-sectional development of 68 infant gut microbiomes and 33 metabolomes were examined with linear mixed models to determine the impact of infant nutrition on gut microbiome taxa and functional development. Nutrition assessments were based on detailed quantitative weighted 3-day food records (months 3,6,9,12) and the intakes of total dietary fiber with its food sources and fiber fractions relied on current internationally approved CODEX-compliant values. Questionnaires were utilized to monitor when various complementary foods were introduced, enabling more comprehensive nutritional analyses. Bacterial species identification was based on MetaPhlAn2 quantification of bacterial species from metagenomic data and metabolomic profiles were generated using four liquid chromatography-mass spectrometry (LC-MS) methods. Results: My examinations place the previously described sequential trajectories in infant gut microbiome maturation into detailed fiber-dependent nutritional context relying on metagenomic species identification. I discovered 176 complementary food derived fiber-bacterial species associations. The majority of the associations (147, 84%) were positive whereas breastfeeding and related variables tended to be inversely associated with the same species, showing strongest inverse correlations to later trajectory species indicative of slower maturation. Both bacterial species and metabolomic profiles displayed pronounced longitudinal shifts in response to solid food fibers. Each introduction of novel dietary source of fiber associated to diversification of the microbiome revealing fiber-species specific temporal patterns. Conclusions: The longitudinal analyses highlight that sufficient fiber intake from appropriate sources during the weaning period likely function to build capacity for the species permanence in the more diverse and stable mature gut microbiome composition and function reached in later childhood.
  • Mäkinen, Hilla (2023)
    Morphological features are considered as markers of microglial functionality, and they show regional heterogeneity in the brain. Recently the sleep-wake cycle was shown to affect microglial morphology in mice and correlate with cortical sleep slow wave activity (SWA). Microglial sizes and ramification increased during the dark period and decreased during the light period in cerebral areas associated with SWA, suggesting that neuronal activation could be affecting microglial morphology through SWA. I studied microglia in the hindbrain areas with and without functional connection to SWA to further investigate the association between SWA and alterations in morphology, and to investigate if there are differences in microglial morphology and their diurnal alterations in brain regions other than those commonly investigated. I examined three hindbrain areas (cerebellar cortex (CC), deep cerebellar nucleus (DCN) and medial vestibular nucleus (MVN)) and somatosensory cortex (SC) of mice (n=15) at two timepoints: 6 hours after the light onset (high SWA) and offset (low SWA). My aims were to answer if there are morphological differences in microglia between 1) the four brain areas at both timepoints and 2) between the two timepoints in each brain area. My hypotheses were that CC and DCN which have functional connections to cortical SWA, would show similar diurnal morphology alterations as demonstrated in the cerebral areas, and MVN that has no known cortical SWA connection, would lack significant alterations. As microglia are heterogenous throughout brain, I expected microglia to differ between different brain areas, especially the hindbrain and the SC. I found that microglial morphologies significantly differed between the hindbrain and the cortex, while the hindbrain areas were more similar in morphology. Moreover, the brain areas demonstrated diurnal morphology alterations of microglia with varying extent: CC and DCN microglial morphology did not correlate with SWA as clearly as SC did, and interestingly, morphological features of MVN microglia showed a pattern opposite to other areas, microglia being larger during the light period than the dark period. These results highlight the importance of the diurnal time to microglial morphology and the heterogeneity of microglia between different brain regions.
  • Asumaa, Nea (2023)
    Diabetes mellitus (DM) is a metabolic disorder, which in 2021 alone affected approximately 537 million adults. DM is a multi-organ disease with several comorbidities, one of which is chronic kidney disease (CKD), which often leads to renal impairment and kidney damage. While current treatment strategies have improved, they fail to protect the kidneys efficiently, which is why further understanding and renoprotective strategies are required. Podocytes are terminally differentiated cells central to the proper function of the glomerular filtration barrier (GFB) in the kidneys, and their injury can lead to the leakage of protein into the primary urine, which is a hallmark of CKD. One of the potential causes of podocyte injury in DM is hyperfiltration induced increase in fluid flow shear stress (FFSS). Podocyte responses to FFSS are still, however, relatively unknown. We exposed cultured human podocytes in vitro to FFSS at 2 dyne/cm2 for 2 hours via a novel flow chamber system. From the FFSS experiments, we studied podocyte motility from live cell imaging, protein expression levels by Western blotting and finally did immunofluorescent labelling to identify protein localizations in the cells. We discovered that podocytes express different modes of motility upon FFSS exposure, notably bleb-like motility previously only described in tumor and embryonic cells. In addition, we observed that podocytes significantly increased the phosphorylation of both AMPK and Ezrin, indicating the activation of pro-survival signalling as well as formation of bleb-like protrusions in response to FFSS stimuli. However, we did not observe significant podocyte loss, indicating that podocytes are capable of withstanding increased FFSS for short exposures such as 60 minutes. We believe that upon FFSS exposure, podocytes activate pro-survival mechanisms such as increased phosphorylation of AMPK and changes in motility in order to better withstand the increased shear stress. However, increased FFSS in for example DM patients is persistent, making it potentially a key factor in the development of podocyte injury and ultimately kidney damage.  
  • Guillon, Melina (2023)
    Faculty: Faculty of Biological and Environmental Sciences Degree programme: Master’s Programme in Neuroscience Study track: Cell and Systems Physiology Author: Mélina GUILLON Title: Inflammatory activation of Macrophages by Triglyceride-Rich Lipoproteins in Atherosclerosis Level: Master’s thesis Month and year: August 2023 Number of pages: 38 Keywords: Atherosclerosis, Inflammation, Triglycerides-Rich Lipoproteins, Emulsion Particles Supervisor or supervisors: Dr. Katariina Öörni Where deposited: Helsinki University Library Additional information: Background: Inflammation is a key factor in atherosclerotic cardiovascular disease (ASCVD) and is present at all phases. It has been shown that reducing inflammation by blocking cytokine pathways diminishes the risk of stroke and myocardial infarction. Despite the well-established linked between lipoproteins and atherosclerosis, little is known on the specific effect of lipids on inflammation. In this study, we investigated the impact of triglycerides-rich lipoproteins’ (TRLs) lipids on inflammation in the context of atherosclerosis. Methods: TRLs were isolated and purified from pooled plasma of healthy volunteers, and emulsion particles (EPs) generated by sonication using lipids extracted from TRLs. TRLs and EPs were characterized in size, triglycerides, and cholesterol content. THP-1 cells were treated with EPs, TRLs, and modified EPs (oxidation, vortexed, and lipolysis with PLA2), and the release of pro-inflammatory cytokines (IL-1β and TNF-α) was detected with ELISA. Results: EPs were successfully synthesized by sonication using an ultrasonic probe. EPs induced cytokine secretion from THP-1 cells (N=4). Modified EPs (Oxidized EPs, vortexed EPs, and PLA2-treated EPs) did not increase cytokine secretion (N=4). Conclusion: Our findings suggest that TRLs’ lipids contribute to inflammation and that TRLs may play a crucial role in the pathogenesis and pathophysiology of ASCVD. Inflammatory properties of TRLs should be extensively investigated in the future for the development of preventive and curative strategies.
  • Jakobsson, Emma (2023)
    The lymphatic system is a network of vessels that permeate a substantial part of the whole body. It plays an essential role in fluid homeostasis by the drainage of interstitial fluid from the blood capillaries, after which the fluid, now called lymph, is transported through the vessel network and back to the blood circulation. The lymphatic system also plays an important role in the transportation of immune cells and in activation and maintenance of the immune system. Due to these crucial functions, there is a growing interest in exploiting the lymphatic system in the treatment of many immunological and inflammatory diseases. In many cases, an ideal treatment method would be to induce lymphatic growth (lymphangiogenesis) to boost immunological functions, facilitate resolution of inflammation and reduce the harm from lymphatic vascular abnormalities. However, there is a gap in knowledge in how to induce lymphangiogenesis in a controlled manner, with the major lymphangiogenic growth factor, vascular endothelial factor C (VEGF-C), tending to create disorganized lymphatic networks. The purpose of this thesis is to investigate factors influencing lymphangiogenesis, in an attempt to find ways to control it. Vaahtomeri research group has preliminary results showing a role of planar cell polarity (PCP) in control of dermal lymphatic vessel sprouting (the initial step for the formation of new lymphatic branches) and lymphatic network expansion. The focus of Vaahtomeri research group has been the core PCP protein Van Gogh-like protein 2 (VANGL2), which together with the other core PCP proteins is known to play an important role in the collective cell polarization and morphogenesis in many tissue types. The role of VANGL2 has previously been studied in the lymphatic system, and so far, VANGL2 has been implicated in both lymphatic valve morphogenesis and in flow-induced control of lymphatic endothelial cell (LEC) polarization. However, there still remains a gap in knowledge in what role VANGL2 plays in lymphangiogenesis and the lymphatic network as a whole. In this thesis, I investigated the role of VANGL2 in lymphangiogenesis, firstly by the use of an in vivo lymph node experiment, which offered a robust model to investigate the role of VANGL2 in the mature lymph node lymphatic network. In the experiment, I induced growth of the lymph node lymphatic network by means of an immunization reaction, and then I compared the lymphatic networks of Vangl2-deleted and control mice. Despite some minor differences between the Vangl2-deleted and control lymphatic networks, this experiment did not show a role for VANGL2 in the mature lymph node lymphatic network. Secondly, I investigated the potential mechanistic role of VANGL2 in control of dermal lymphatic vessel sprouting in growth conditions. This experiment showed a specific role for VANGL2 in sprouting of the lymphatic network, thus providing valuable research in understanding how lymphangiogenesis is regulated. Altogether, the results presented in this thesis work as a steppingstone for finding new treatments relating to the safe induction of lymphangiogenesis.
  • Ilkka, Liisa (2023)
    After decades of lull, the use of psychedelics as therapeutical agents has regained both scientific and public attention. The so-called classical psychedelics are currently studied in the treatment of multiple psychiatric conditions, including addiction. The current understanding implies that psychedelics mediate their subjective effects through serotonergic 5-HT2A receptor binding. The activation of the receptor also leads to increases in brainderived neurotrophic factor (BDNF) expression, a critical part of neuroplasticity mechanisms. At a behavioral level, facilitated neuroplasticity can be observed for example as quicker learning. Because addiction often involves associative learning between the pleasure produced by the drug use and the environmental cues, learning away from these associations could help to prevent relapses and enhance recovery. In this study we aimed to assess LSD’s effect on BDNF levels in amygdalar and cortical regions, and their connection to extinction learning in fear and conditioned place preference paradigms. To evaluate time window for enhanced neuroplasticity, we chose two time points for BDNF level measurement, 24 and 48 h after the LSD injections. In addition, we chose both male and female mice for behavioral experiments to study possible differences between the sexes. We did not observe statistically significant differences between the treatment groups in BDNF levels or behavioral experiments after the single LSD injections. Despite that, this study provides perspectives for improving the experimental setups, as well as helps to evaluate still unanswered questions around the connection between psychedelics and neuroplasticity.
  • Vara, Saimi (2023)
    In this thesis, I studied T cell responses to SARS-CoV-2 structural proteins in subjects who had been both vaccinated and infected (n=30), who had only been infected (n=22), and as controls, in subjects who had been neither vaccinated nor infected (n=6). In addition, I compared cellular responses between groups of subjects who had been infected with either wild-type (WT) SARS-CoV-2, Alpha (B.1.1.7), or Beta (B.1.351) variants. Before analyzing the samples to be studied, I optimized the conditions for the cell stimulations. Peripheral blood mononuclear cells (PBMCs) were collected from infected subjects six months after infection. PBMCs were stimulated with SARS-CoV-2 wild-type nucleoprotein, spike-, envelope-, and membrane protein peptide pools. I quantified cytokines and effector molecules characteristic of CD4+ and CD8+ cell responses; perforin, tumor necrosis factor alpha (TNF-a), granzyme B, interferon gamma (IFN-γ), interleukin 2 (IL-2) and interleukin 4 (IL-4) secreted by PBMCs were quantified. In this study, I found that subjects with infection, or combination of infection and vaccination had higher cellular immune responses compared to uninfected controls. Infection induced higher granzyme B, IFN-y, and IL-2 secretion, and the combination of infection and vaccination induced higher granzyme B, perforin, IFN-y, IL-2 and IL-4 secretion. I found that subjects with hybrid immunity, defined as immunity acquired from combined vaccination and infection, had on average higher IL-4 responses compared to those who had been infected only. In this study, I found that nucleoprotein, spike-, and membrane proteins stimulated T cell responses whereas envelope protein did not stimulate T cell responses. I found that WT, Alpha or Beta infection produced equally good T cell responses to WT spike peptide. In conclusion, I found that COVID-19 patients have long-lasting T cell responses. I found that T cells recognize different SARS-CoV-2 variants. Mutations present in the spike proteins of the different variants do not affect T-cell ability to recognize these antigens. Immunity based on T cells is not as susceptible to antigenic changes as the humoral immunity. T cells have a vital role in protection against variants, when new SARS-CoV-2 variants evaded antibody-based immunity.