Browsing by master's degree program "Neurotieteen maisteriohjelma"

4-Methylmethcathinone (Mephedrone) is one of the the most prevalent synthetic cathinones that bears close structural similarity to amphetamines. Like other stimulants, mephedrone is often used with alcohol (ethanol). In animal studies ethanol has been observed to potentiate the neurotoxicity of amphetamine-type stimulants, and same has been observed when mephedrone and alcohol is combined. The long-term effects of mephedrone have still remained largely elusive. The aim of this thesis is to study the effects of mephedrone, methamphetamine, and ethanol on dendritic spine density and morphology in the hippocampus, nucleus accumbens and caudate putamen, and compare the spine densities with changes in brain activation observed in manganese-enhanced magnetic resonance imaging (MEMRI). Dendritic spines are small membranous protrusions on dendrites that act as the post-synaptic sites for most of the excitatory synapses. Amphetamine and methamphetamine have been shown to affect the density and morphology of the spines. The goal of this thesis was to investigate the long-term effect of binge-like (two times a day, four consecutive days) stimulant treatment on dendritic spines using Golgi-stained rat brain sections. The brains of 48 male Wistar rats were imaged using AxioImager Z2 microscope and the number and the size of the spines was analyzed using Reconstruct software. In this thesis no effect on dendritic spines was observed in the hippocampus and nucleus accumbens in animals treated with mephedrone, methamphetamine, ethanol or combination of them. In the caudate putamen significant increase in the total density of dendritic spines and in the density of filopodia-like spines was observed in mephedrone-treated animals. Other treatments showed no observable effect. These results were conflicting with previous studies where amphetamine-type stimulants have been shown to increase the spine density in the nucleus accumbens and the hippocampus and increase the density of branched spines. In the caudate putamen methamphetamine has been observed to decrease the spine density. There was no correlation between spine densities and brain activation observed in MEMRI. To my best knowledge this is the first time when the effect of mephedrone on dendritic spines has been studied. It is possible that the treatment regimen used here was not strong enough to produce marked long-term changes on dendritic spines. It is also possible, that mephedrone is not as neurotoxic as other amphetamine-type stimulants, which may explain why the effects remained limited and conflicting. More research is still required to establish the long-term structural effects of mephedrone.

Environmental enrichment (EE) can be defined as external stimulation by the physical or social surroundings. Like antidepressants, EE promotes neuronal plasticity in the brain, although the exact mechanisms of action are unknown. The aim of these experiments was to further elucidate the role of BDNF-TrkB in the behavioural outcomes of EE exposure. The effect of 10 weeks of environmental enrichment on neuroplasticity was investigated in female wildtype, BDNF-het, and hTrkB-Y433F mutant mice. Behavioural tests, open field, elevated plus maze, and novel object recognition, were conducted to assess memory, learning, and anxiety-like behaviour. Results were analysed in Excel and GraphPad Prism 9.0. with two-way ANOVA and Šídak’s posthoc test. EE affected the OF behaviour of WT and hTrkB-Y433F mice, but not BDNF-het mice. EE brought BDNF-het mice behaviour to the level of WT. Two-way ANOVA indicated that environment was the primary contributor for difference in results, as opposed to genotype. EE did not have a significant effect on EPM or NOR results in either mutant genotype. These results indicate that the BDNF-TrkB pathway, but not the TrkB receptor itself, plays a role in generating behavioural effects of EE. Further study is needed to elucidate the molecular mechanisms behind EE effect on plasticity. Studies separating components of EE would be interesting to see if any exhibit a stronger plasticity effect. Comparison of EE with other known plasticity promoters, ie: antidepressants and rapid-acting antidepressants, would be interesting particularly at a mechanistic level.

Finnish matriculation examination in biology transitioned into a digital examination from traditional pen-and-paper examination in spring of 2018 as a part of larger process aiming to digitalize the entire matriculation examination. Tthe requirements for the exam have also changed: in addition to subject knowledge, the digital examination also requires the candidate to also be master the digital skills outlined in the Finnish high school curriculum, for example the use of image- and data processing programs. It has been suggested hat candidates from higher socioeconomic background benefit more from digital skill teaching. It has also been shown that some teachers overestimate the digital skills of the students, omitting parts of the teaching process that are integral for learning. Tthis study examines whether the matriculation examination answers requiring digital skills differ from questions that can be answered without advanced digital skills. Statistically significantly worse performance in questions requiring digital skills might indicate digital skill teaching that is insufficient compared to the skill level required in matriculation examination. Insufficient teaching may disproportionately affect those from lower socioeconomic background. The data of this study consists of 30 full-length answers from matriculation examinations of spring 2018, autumn 2018 and spring 2019, for a total of 90 full-length answers. The data was a randomized sample provided by Ylioppilastutkintolautakunta (Finnish Matriculation Examination Board). The differences were analysed with Mann-Whitney U-test and Fisher’s z-transformation. The study found that questions requiring digital skills were statistically significantly more popular than questions that didn’t require digital skills. Although the level of cognitive processing outlined by Bloom’s Taxonomy was lower in questions requiring digital skills, there was no statistically significant difference in the success (measured by attained score) between the answers. According to results, the digital proficiency of the candidates was at a sufficient level to answer to the questions.. The study also speculates on factors that could explain the observed differences in answer popularity, cognitive depth and difficulty level of the questions.

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.  

White matter (WM) structural connectivity alterations have been linked to depression. This study aimed to identify structural connectivity metrics associated with Major depressive disorder (MDD) and predictive of different symptom phenotypes. The study sample included N=29 control and N=86 subjects with MDD who underwent a clinical interview, Mini-International Neuropsychiatric Interview (MINI), and assessment of depression symptoms severity. Using a 3T MRI scanner, diffusion tensor imaging (DTI) was employed to capture WM connectivity markers at baseline. While no distinct differences between control and MDD groups were observed at the whole-brain network level, significant alterations were evident at the node level. Clinical group demonstrated enhanced connectivity, particularly in the DefaultB and LimbicB subsystems, as evidenced by measures such as eigenvector centrality. Furthermore, notable differences were observed in clustering coefficient and local efficiency, predominantly in DefaultB, LimbicB, and VisPeri networks, with MDD patients showing higher connectivity. Analysis of the association between WM structural connectivity measures, both global (e.g. global efficiency) and local (e.g. clustering coefficient) with MDD symptom scores and related symptoms, revealed no significant correlation at the whole-brain level, both at baseline and post-intervention. Distinct patterns were identified when evaluating node-level metrics averaged across networks, which together with group differences, point to MDD patients exhibiting characteristics consistent with regular networks. Hierarchical clustering based on standardized baseline DTI structural connectivity within the clinical cohort revealed three distinct clusters of MDD patients, with the first cluster exhibiting a higher WHO-5 score, indicating a potential association with better well-being. These findings provide insight into MDD-specific brain regions’ structural alterations and underscore the heterogeneity of depression symptom profiles. Further research is needed, including a higher sample size and control for confounding factors.

Women have exhibited higher levels of math anxiety (MA) compared to men. Despite the relationship between MA and sex differences being topic of interest for over twenty years, the focal point has mostly been on the psychological causes. This review investigates the biological underpinnings of the social phobia and identifies numerous possible correlates which could inform future efforts to support students experiencing math anxiety and encourage more females to pursue STEM related careers. Articles that investigated sex differences in the context of MA were selected for the study using PRISMA guidelines. Females were found to experience higher levels of math anxiety compared to males. Age was shown to influence the prevalence of MA between sexes, with sex differences in MA being more infrequent in children and increasing towards adulthood. The findings suggest that a diverse set of biological sex differences related to to brain function, cognition and sex hormones can, in part, explain the higher prevalence of MA among females and age-related deviations. By shedding light on possible biological factors contributing to sex differences in MA, this review represents a valuable step toward a more comprehensive understanding of this complex issue.

Dermatologia on visuaalisia taitoja vaativa lääketieteen osa-alue, joka tutkii iholla, päänahassa, hiuksissa ja kynsissä esiintyviä sairauksia ja syöpiä. Ihotautien diagnosointi vaatii visuaalista asiantuntijuutta, joka tarkoittaa kykyä tehdä havaintoja ja tulkita niitä tarkoituksenmukaisesti. Asiantuntijuus syntyy havainto-oppimisesta, joka perustuu kokemuksen kautta kehittyneeseen kykyyn erotella ja luokitella tietoa. Se tarkoittaa kykyä erottaa olennainen epäolennaisesta, yhdistellä tietoa ja niiden välisiä suhteita sekä käsitellä poimittua tietoa nopeammin ja tehokkaammin. Visuaalista tarkkuutta vaativilla aloilla silmänliikkeiden tutkiminen voi paljastaa lääketieteellisten taitojen taustalla vaikuttavia ajatusprosesseja sekä oppimiseen liittyviä mekanismeja. Silmänliikkeiden ja digitaalisten havainto-oppimismoduulien yhdistäminen voi tarjota hyödyllistä tietoa visuaalisen asiantuntijuuden kehittymisestä ja auttaa suunnittelemaan toimivampia opetusmenetelmiä. Digitaalisista oppimismoduuleista saatu tutkimustieto on tarjonnut viitteitä siitä, että ne vaikuttavat positiivisesti visuaalisiin taitoihin. Tässä tutkimuksessa tutkittiin Helsingin yliopiston lääketieteen perustutkinto-opiskelijoiden visuaalisen asiantuntijuuden kehittymistä ihotautikurssin ja havainto-oppimismoduulien avulla. Opiskelijat (N = 63) tekivät ihotautikurssin yhteydessä kahta erilaista digitaalista havainto-oppimismoduulia, jotka sisälsivät kliinisiä ihotautikuvia. Niiden avulla tutkittavien tuli tunnistaa kuvissa esiintyvät ihosairaudet niistä näkyvien piirteiden perusteella. Suoriutumista mitattiin onnistumisprosentin, vastausajan ja varmuuden perusteella. Pienempään osaotokseen osallistui 13 opiskelijaa ja 7 ihotauteihin erikoistunutta lääkäriä. Suoriutumisen lisäksi tallennettiin heidän silmänliikkeensä (fiksaatioiden määrä, kesto ja sijainti), jotta nähtäisiin, mihin heidän katseensa kiinnittyy moduulien tekemisen aikana. Lopuksi opiskelijoiden ja asiantuntijoiden tuloksia verrattiin keskenään. Tulokset osoittivat, että opiskelijat suoriutuivat kohtalaisen hyvin moduuleissa kurssin alussa, mutta erot asiantuntijoihin olivat suuria. Visuaalisessa prosessoinnissa (fiksaatioiden määrä, kesto ja sijainti) eroja oli erityisesti fiksaatioiden määrässä: opiskelijoilla oli selvästi enemmän fiksaatioita kuin asiantuntijoilla. Kurssin lopussa opiskelijoiden ja asiantuntijoiden väliset erot suoriutumisessa pienenivät merkittävästi ja visuaalisessa prosessoinnissa eroja ei ollut enää lainkaan. Tutkimus osoitti, että opiskelijoiden visuaalinen asiantuntijuus kehittyi kurssin aikana ja havainto-oppimismoduulit olivat hyödyllinen opetusväline dermatologian opetuksessa. Toimivien opetusmenetelmien kehittäminen on tärkeää, jotta ne tukisivat opiskelijoiden oppimista ja visuaalisen asiantuntijuuden kehittymistä. Opiskelijoiden diagnoositarkkuuden ja kliinisen päättelykyvyn tehostuminen voisivat vähentää aikaisemmissa tutkimuksissa havaittuja eroja eksperttien ja noviisien välillä.

Education research has for decades acknowledged that prior knowledge is a strong predictor of academic success. This idea is largely based on constructivist theory of learning which postulates that all learning occurs by actively building on existing knowledge. When this prior knowledge conflicts with the normative scientific understanding, students are dealing with incompatible knowledge structures, or misconceptions. Misconceptions need to be revised and sometimes even replaced through a learning process called conceptual change. Research shows that the level of prior knowledge can determine students’ academic success and performance. Undergraduate biology students enrol to university with diverse levels of prior knowledge and concepts regarding topics such as photosynthesis, cellular respiration, primary production in ecosystems, and Darwinian evolution. These topics present challenges for learning because of their complexity. At the same time, a robust understanding of them is essential. These topics are at the heart of mitigating and resolving the climate crisis and other global natural threats. This study explored the level of prior knowledge and the nature of misconceptions held by undergraduate biology students at the beginning of their academic degree in fall of 2019, and further sought to describe how their conceptual understanding developed during the first academic year. Students (N = 41) completed a questionnaire consisting of eight open-ended questions that were designed to assess declarative knowledge of facts and meaning, and procedural integration and application of knowledge. This pre-test measurement was conducted in September 2019. In the post-test measurement, the same questionnaire was repeated a year later. The data were analysed with a mixed methods approach where the answers were quantitatively scored as well as qualitatively analysed for misconceptions. The qualitative content analysis of the answers relied both on existing literature and on the content of the answers themselves. Results showed that the students’ prior knowledge was relatively poor in the beginning of their studies. Most students performed well in tasks measuring knowledge of facts and meaning but struggled in tasks measuring integration and application of knowledge. During the first academic year, the students’ understanding generally improved as demonstrated by the improvement in mean scores of the tasks. Misconceptions were robust and pervasive. The most pervasive misconceptions reflected difficulties in understanding emergent properties and processes. Misconceptions related to the process of Darwinian evolution became more prominent in the post-test. Persistent misconceptions became integrated with the new conceptual frameworks that the students acquired during the first academic year. If students held no misconceptions in the post-test, they performed significantly better in both tests than those with misconceptions. During this first academic year learning seemed to be mainly additive as conceptual change turned out to be rare. The need for more encompassing biology teaching at least in the University of Helsinki became evident. Introductory courses should acknowledge the large degree of variation in students’ prior knowledge and assess the most common and serious misconceptions even over course theme disciplines to ensure more equal learning outcomes.

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.

This thesis explores the relationship between neuropathic pain and the circadian clock through the investigation of GSK4112 administration to a mouse model of neuropathic pain. Neuropathic pain, arising from a lesion or disease of the somatosensory system, historically posed treatment challenges due to narrow research approaches focusing solely on the pain system. Recent insights highlight connections between neuropathic pain and the circadian clock, including circadian rhythmicity in neuropathic pain and shared genetic expressions and pathways. The study aimed to investigate the effects of GSK4112, an agonist of Rev-erbα and a small molecule modulator of the circadian clock. This was done through a blinded experiment design in mice modelling neuropathic pain induced by spared nerve injury. The study involved tracking locomotive activity to assess alterations in circadian rhythm and infer effects on the circadian clock. In addition, behavioural tests that measure mechanical and thermal sensitivity were employed to investigate the potential analgesic effects of GSK4112 administration. As a result, no change to circadian activity or mechanical and thermal sensitivity was observed as a result of GSK4112 administration to mice with spared nerve injury.