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Browsing by master's degree program "Neurotieteen maisteriohjelma"

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  • Knapič, Samanta (2023)
    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.
  • de Sena, Sofie (2022)
    The analysis of gaze behaviour is nowadays commonly employed to help with the diagnosis and exclusion of differential neurological conditions as well as to help researchers better understand cognition in the early stages of life. However, its application in the developmental evaluation and follow-up of children with early-onset epilepsy has not been profoundly studied yet. Therefore, the current study aimed to investigate the association between the gaze behaviour of infants with early-onset epilepsy and their future neurodevelopmental outcome. To study the association and its predictive ability, three models were created. Sixty-three infants with epileptic seizure onset before 12 months of age participated in the study with the voluntary consent of their parents. Infants’ gaze behaviour was recorded with Tobii Pro-X3-120 at two measure points. The results showed infants’ initial ability to fixate their gaze, changes in their gaze shift probability in the first 12 months of life, and structural aetiology to be significantly associated with the infants' developmental outcome at 24 months of age. Where the structural aetiology was significantly associated with poorer developmental outcome, good initial fixation ability and improvements in the infants’ gaze shift probability during their first year of life were significantly associated with more positive outcome. These findings suggest that gaze behaviour at an early age is an essential predictor of later development in infants with early-onset epilepsy. Hence, eye-tracking could provide means to evaluate the later neurocognitive outcome of infants with early-onset epilepsy at an early age.
  • Kuoppalaakso, Timo (2023)
    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.
  • Grönlund, Katja (2023)
    Nuclear receptor subfamily 5 group A member 1 (NR5A1) is a master regulator of both steroidogenesis and gonadal development. Disruptions of NR5A1 can result in differences in sexual development (DSD). With proven interspecies differences in NR5A1 functioning and human material not being available, human stem cells are one of the most achievable, ethical, and accurate models to study the earliest developmental stages of foetal life. However, in currently existing human stem cell-derived gonadal models the expression of NR5A1 has been insufficient without artificial induction due to the lack of knowledge of its distinct biological mechanisms, endogenous ligands, and co-factors. A functional reporter cell line would enable high throughput microscope screening of differentiation protocols with expressed NR5A1. The aim of this thesis was to generate a functional monoclonal human embryonic stem cell (hESC) reporter line for the gene NR5A1 with Alt-R CRISPR-Cas9 ribonucleoprotein (RNP) complex. Firstly, an efficient guide RNA was determined for NR5A1 by T7 assay, and a homology-directed repair (HDR) donor plasmid was designed based on it. Secondly, monoclonal hESC lines were generated with the Alt-R CRISPR-Cas9 RNP complex knock-in method and HDR donor plasmid via electroporation and single-cell sorting. Finally, monoclonal hESC reporter lines were screened with Touchdown PCR and a functionality analysis based on fluorescence and mRNA expression was performed. Two monoclonal hESC reporter lines H9-NR5A1-eGFP cl. 1 and dual-inducible H9-NR5A1-DDdCas9VP192-eGFP cl. 28 were established by using Alt-R CRISPR-Cas9 RNP complex. However, a functional validation performed on H9-NR5A1-DDdCas9VP192-eGFP cl. 28 cells showed the cell line to be non-functional upon NR5A1 upregulation regardless of the expressed eGFP mRNA detected with RT-qPCR.
  • Junell, Niklas (2021)
    Hippocampal place fields play a key role in spatial navigation. New place fields are formed during exploratory behavior through long-term potentiation (LTP) and long-term depression (LTD) of synaptic inputs to place cells located in hippocampal CA1. Recently, a novel form synaptic plasticity termed behavioral time scale plasticity (BTSP) has been demonstrated to occur in CA3–CA1 synapses in vitro. BTSP can potentiate synapses that were active several hundred milliseconds before or after a priming event such as a strong and prolonged somatic depolarization. This plasticity rule could be an important complement to well-established spike timing dependent plasticity (STDP) which associates neuronal inputs with outputs at a time scale less than a few tens of milliseconds. The aim of this thesis was to determine whether high frequency antidromic stimulation can act as a priming event that enables BTSP induction in CA1 pyramidal neurons. The underlying assumption was that antidromic stimulation could prime BTSP via action potential backpropagation. High frequency bursting of CA1 neurons in hippocampal slices was achieved with 100 Hz antidromic stimulation of CA1 axons in the alveus. Schaffer collaterals were stimulated 500 ms before or after CA1 burst firing with intensities that were subthreshold for LTP when unpaired. I found that high frequency firing did not enable LTP induction during either of the two experimental protocols, suggesting that neuronal output alone is insufficient for priming BTSP.
  • Kiviluoma, Tomi (2021)
    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.
  • Kontio, Salla (2022)
    Spontaneous and voluntary movements of infants effectively reflect the developmental integrity of brain networks. When it comes to the research of motor development, the use of intelligent technology has shown to provide objective, automated, and scalable methods for movement assessment. In addition to intelligent technology, research on the usage of surveys – in this case parental surveys – has looked at the untapped potential that parental viewpoint. Guardians have a unique and holistic image of the child’s development, thus data from parental surveys could be used to further help us to assess infant’s development. For this study, I studied how the parents’ time estimate on the positions their child spends time in holds up against the machine-learning based data obtained with the smart jumpsuit. Using the data acquired from the smart jumpsuit during the recordings, we can see the amount of time the child spends in each position. Aim was to study the relationship between these variables and gain further understanding on the utilization of parental perspective in the assessment of motor development. Data was collected from 19 video recordings and videos were annotated with Anvil video annotation software for child’s posture and movements, and the annotations were used for training a machine learning-based classifier of the smart jumpsuit. Only data regarding postures was extracted for further analysis. Parental surveys were carried alongside of recordings. In the survey of parental estimate, we asked the parent to assess how much time the child spends in a specific posture. Positions which the survey focused on were prone, supine, side, sitting, crawling, and standing. Data from the recordings as well as data from parental surveys were visualized with radar plots. In addition, correlation was visualized in a linear regression. Positions which had both correlation of higher than 0.5 and a significant p-value were sitting (p < .001**), crawl posture (p < .05*), standing (p < .001**), and supine (p < .05*). Results suggested that parents were successfully assess the time spent in following postures: sitting, crawling, standing, and supine. This indicates that parents have a holistic understanding of their child’s motor development, and the knowledge could be useful in the overall assessment of development, especially when it comes to children with developmental delay. The parent’s ability to accurately assess a child’s motor development helps the parent support the child’s development.
  • 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.
  • Kõbin, Mihkel (2020)
    Intersectins (ITSNs) are important scaffold and adaptor proteins that play an important role in various cellular processes such as endocytosis. Although we know a lot about their function, there is little information on the regulation of these proteins. On the other hand, microRNAs have been shown to have an extensive function in regulating numerous genes in animals and their dysfunction is credited for down regulation of many proteins. In this study, I demonstrate that microRNAs are potential regulators of ITSNs in HEK293 cells and human neuronal cell cultures. In this study, I cloned 3’UTRs of different isoforms of intersectins (ITSNs) and microRNAs to the expression vectors to express them in cells. I then transfected HEK293T or neuronal stem cell line (HEL47.2) with the constructed vectors and used various methods to analyse the effect of microRNAs on the expression of ITSNs. The main methods I used were dual-luciferase assay, reverse transcription quantitative PCR and western blotting, human neuronal stem cell culturing and lentiviral transduction. My results demonstrate that there were two microRNAs that stood out from other and had a significant downregulation of ITSNs mRNA levels in HEK293T cells. Those were miR-124 and miR-19. However, in the human neuronal cell line I did not observe a significant alteration of the ITSNs transcript level. Additionally, I suggest that the given microRNAs regulate protein levels by promoting the decay of the ITSN transcripts. However, more studies are needed to show a stronger causative effect of microRNAs on ITSNs. Subsequent studies should also look at how multiple microRNAs can influence gene expression cooperatively.
  • Ruuska, Janika (2022)
    Individuals suffering from anorexia nervosa (AN) have one of the highest mortality rates of all psychiatric disorders, as a consequence of health complications that follows severe malnutrition. The impairments in cognitive flexibility, including an extreme focus on restricting food despite a rapid decline in body weight in AN, also plays an important role in the development of the disorder and has been suggested as a hallmark of AN. This cognitive inflexibility, common among many psychiatric disorders such as depression and obsessive-compulsive disorder, is linked to alterations in serotonin (5-HT) signaling in the medial prefrontal cortex (mPFC). Reduced 5-HT2A receptor activity and potentially increased 5-HT1A receptor activity are evident in the mPFC in individuals with AN and may be linked to impaired cognitive flexibility, however, the mechanisms through which 5-HT and inflexibility interact in AN are not fully understood. A better understanding of this link could pave the way toward more effective pharmacological treatments for AN. Psilocybin, a psychedelic compound produced by so-called “magic” mushrooms, has a high affinity for several 5-HT receptor subtypes including 5-HT1A and 5-HT2A receptors, and has now been empirically demonstrated to increase cognitive flexibility in individuals with major depressive disorder (MDD). In this study, we sought to understand how the development of pathological weight loss and/or psilocybin administration influenced the expression of RNA molecules of 5-HT2A and 5-HT1A receptors expression in the mPFC of rats. To this end, we used the activity-based anorexia (ABA) model, the only experimental model known to elicit voluntary reductions in food intake and voluntary hyperactivity that leads to rapid body weight loss in the majority of animals exposed to ABA conditions. Outcomes were compared against an age-matched control group that were not exposed to the ABA paradigm. Animals were administered psilocybin (1.5 mg/kg) or saline (control) and 4-10 days later brain tissue was collected for processing. Receptor expression was detected using a novel multiplex RNA fluorescent in situ hybridization (FISH) technology, RNAscope®. The main aim of this study was to examine changes in the expression of RNA molecules of 5-HT2A and 5-HT1A receptors in the mPFC elicited by ABA conditions and determine whether these were ameliorated by the administration of psilocybin. We found that animals exposed to ABA demonstrated a significant reduction of 5-HT2A receptors’ RNA levels in the mPFC, and that this was not influenced by psilocybin treatment. There have been reports from clinical trials that individuals with AN experience “less than expected” subjective effects from psilocybin, which may be explained by reduced expression of RNA molecules of 5-HT2A receptors in the mPFC, and is supported by our results in rats. Taken together, these results highlight a specific serotonergic mechanism that could underly the development of pathological weight loss and offers insight into possible issues with the therapeutic application of psilocybin for AN. Future studies will need to examine the effects of psilocybin during a more acute period following treatment to define these effects. Moreover, whether or not the reduced 5- HT2A receptors’ RNA level expression induced by ABA is restored with body weight recovery should be determined.
  • Luoto, Senni (2021)
    Kalvojännitteen syntyyn ja sen muutoksiin liittyvät prosessit mielletään usein haastaviksi aiheiksi oppia ja opettaa. Aiheen opetuksesta ja oppimisesta lukiossa ei juurikaan ole tehty tutkimusta, mutta aiemmat tutkimukset yliopisto-opiskelijoilla ovat osoittaneet, että haasteita esiintyy erityisesti lepokalvojännitteen muodostumisen ymmärtämisessä. Aihetta käsitellään suomalaisissa lukiossa pääasiassa ihmisen biologian kontekstissa vapaavalintaisella kurssilla 4 (LOPS 2015) tai 5 (LOPS 2019) ja aihe onkin yksi ihmisen biologian kurssin keskeisistä sisällöistä oppia ja ymmärtää. Kalvojännitteen synty ja sen muutokset on kuvattu suomenkielisissä lukion biologian oppikirjoissa usein yksinkertais-tetusti ja ajoittain virheellisesti. Tämä saattaa johtaa virhekäsitysten syntymiseen, jolloin opiskeltavaa aihetta ei opita riittävällä tasolla. Siksi tämän maisterintutkielman tavoitteena on selvittää, miten solukalvon sähköistä aktiivisuutta opetetaan suomenkielisissä lukioissa ja millaisia virhekäsityksiä opiskelijoilla aiheesta esiintyy. Näiden tulosten pohjal-ta luodaan kehittämistuotos eli opetusmateriaali biologian aineenopettajien käyttöön, jolla voidaan tukea solukalvon sähköisen aktiivisuuden opetusta ja oppimista. Tutkimusmenetelmänä tutkimuksessa käytettiin kehittämistutkimusta, jossa yhdisteltiin teoreettisen ja empiirisen ongelma-analyysin periaatteita. Teoreettisen ongelma-analyysin kautta pyrittiin kartoittamaan lukio-opetuksen kannalta solukalvon sähköiseen toimintaan liittyvät keskeisimmät seikat, joihin monet virhekäsitykset liittyvät, sekä tarkastelemaan niitä eri näkökulmista. Tämä toteutettiin aiemman tutkimuskirjallisuuden avulla. Empiirisessä ongelma-analyysissä tarkasteltiin sekä lukion biologian oppikirjoja (N=3) että kevään 2021 biologian ylioppilaskoevastauksia (N=400) hermosolun aktiopotentiaalin kulkuun liittyen. Molempia aineistoja analysoitiin laadullisen sisällönanalyysin periaatteiden mukaisesti. Teoreettisesta ja empiirisestä ongelma-analyysistä saatujen tulosten perusteella kehitettiin opetusmateriaalin ensimmäinen versio. Opetusmateriaali luetutettiin läpi maisterintutkielman ohjaajilla ja opetusmateriaalia kehitettiin heiltä saatujen kommenttien perusteella. Jatkokehittämisen tuloksena syntyi opetusmateriaalin toinen ja virallinen versio. Tutkimuksen tulokset osoittivat, että solukalvon sähköinen aktiivisuus on haastava aihe sekä opetuksen että oppimi-sen näkökulmasta. Lukion biologian oppikirjoissa esiintyi epätarkkoja kohtia solukalvon sähköiseen aktiivisuuteen liit-tyen ja nämä epätarkkuudet näkyivät opiskelijoiden ylioppilaskokeen vastauksissa yleisinä virhekäsityksinä. Erityisesti esiin nousi virheellinen käsitys natrium-kaliumpumpun ioneja ”palauttavasta” vaikutuksesta aktiopotentiaalin jälkeen. Toinen yleinen virhekäsitys oli, että uusi aktiopotentiaali on mahdollinen vasta kun kalvojännite on hyperpolarisaation jälkeen palautunut lepotilaan. Tulosten perusteella voidaan todeta, että ainakin osa opiskelijoiden virhekäsityksistä on lähtöisin oppikirjoista eikä näitä virhekäsityksiä ole pystytty korjaamaan opettajan toimesta opetustilanteessa. Ylioppi-laskokeessa tehtävään vastanneista opiskelijoista 11,3 % ei osannut vastata tehtävän ensimmäiseen kysymykseen ollenkaan. Vastauksista, joissa opiskelija oli vähintään välttävällä tasolla onnistunut vastaamaan kysymykseen (N=381), 92,4 % sisälsi yhden tai useamman virhekäsityksen. Virhekäsitysten karsimiseksi paras keino on estää niiden syntyminen. Siksi tämän tutkimuksen perusteella voidaan todeta, että lukion uuden opetussuunnitelman biologian oppikirjat tulisi päivittää sellaisiksi, että virheellistä käsitystä ei pääse syntymään. Tämä ei kuitenkaan pelkästään riitä, vaan myös lukion biologian opettajien tulisi luopua vanhoista opetusdioistaan ja varmistaa, että he opettavat aihetta nykytiedon valossa oikein. Tässä apuna toimii tämän tutkimuksen osana kehitetty opetusmateriaali solukalvon sähköisestä aktiivisuudesta hermosolun aktiopotentiaalin kontekstissa. Jotta opetusmateriaalin toimivuutta ja opiskelijoiden käsitteellistä muutosta voidaan arvioida, jatkotutkimukset ai-heesta ovat tarpeellisia.
  • Nurmi, Joonas (2022)
    Goal-directed behavior is reliant on the ability to choose correct actions to perform given the context of the situation while minimizing the interfering effect of goal-irrelevant stimuli. The ability to suppress inappropriate responses is called response inhibition. It can be seen as a higher order cognitive function which is one of the cornerstones for adaptive behavior in ever changing environment. Neural oscillations have been previously used to study at the neuronal processes underlying cognitive processes such as response inhibition. Neural oscillations are rhythmic fluctuation in the excitability of a neuron or a group of neurons. These temporal windows of excitability are thought to underlie efficient communication by changing the efficacy of the synaptic transmissions between neurons/group of neurons. Although, a lot has been uncovered about the different oscillations and their possible role in response inhibition, very little is known how the spectral content (power of a frequency) adapts across as the animal is learning to suppress their responses to new novel stimuli. This kind of learning associated spectral content adaptations has been observed previously in humans during motor learning for example. In the current study we aimed to look how spectral content adapts as the animals learn to suppress their responses to novel stimuli. We used head fixed rats on a treadmill that were trained to perform Go/NoGo task. Each rat performed 1-4 learning scenarios during which the “rules” for Go/NoGo task changes in an attentional set-shifting paradigm. We measured EEG from most of the rat’s cortex. EEG was measured from the point where the rat was first introduced to these novel stimuli until the rat had learned the new stimulus-response contingences. This EEG was divided into learning stages and the power spectrum was calculated for each of them. We observed power peaks centered around 1Hz, 2Hz, 4Hz, 8Hz and 11Hz across learning stages. However further analyses comparing average power across learning stages showed that these changes were not statistically significant. Thus, we did not observe gradual changes in power while rats were learning to suppress their responses to novel stimuli.
  • Nykänen, Heidi (2022)
    Parkinsonin tauti on maailman yleisin hermorappeumaa aiheuttava liikehäiriösairaus. Taudin ilmaantuvuus- ja esiintyvyysluvut ovat jatkuvassa nousussa, mitä väestön ikääntyminen ei yksin selitä. Taudin patologisia löydöksiä ovat alfasynukleiinin kertyminen ja vääränlaisesta laskostumisesta johtuva aggregaatio, Lewy neuriittien ja kappaleiden kertyminen sekä dopaminergisten hermosolujen solukato mustatumakkeesta. Taudin pidemmälle edenneille vaiheille on tyypillistä vaikea toimintakyvyttömyys ja elinajanodotteen lasku. Nykyiset hoitomuodot niin Parkinsonin taudille, kuin muillekin hermorappeumasairauksille ovat ainoastaan oireita lievittäviä. Onnistuneeseen lääkekehitykseen vaaditaan parannusta eläinmallien validiteetin jokaisella alatasolla. Parkinsonin taudin käytössä olevissa prekliinisissä eläinmalleissa on huono ilmivaliditeetti monien potilailla tehtyjen patologisten löydösten puuttuessa. Tässä tutkielmassa esitän uudenlaisen SynFib rottamallin Parkinsonin tautiin. Eksogeenisesti valmistettuja ihmisen alfasynukleiinifibrillejä injisoitiin yhdessä alfasynukleiinia ekspressoivien virusvektoreiden kanssa mustatumakkeeseen. Injektio aiheutti intensiivisen ja etenevän alfasynukleiinista johtuvan patologian ja merkittävän dopaminergisen soluvaurion. Taudin etenemistä seurattiin pitkittäistutkimuksessa positroniemissiotomografialla ja toiminnallisia puutteita arvioitiin synapsitiheydessä, inflammaatiossa ja dopaminergisessa järjestelmässä 16 viikon ajan. Havaitsin aivokudoksen tulehduksen ja dopaminergisen ipsilateraalisen soluvaurion lisääntyneen merkittävästi. Kahden viikon kohdalla synapsitiheys oli merkittävästi vähentynyt ipsilateraalisesti ja taudin leviäminen kontralateraaliselle puolelle oli alkanut.
  • Haapala, Anu Johanna (2023)
    Introduction: Oxidative stress occurs in cells when reactive oxygen species are generated as a by-product of oxygen metabolism and start to accumulate excessively. While extensive oxidative stress is highly detrimental to the cells, trophic factors help them survive. Trophic factor MANF has interested especially Parkinson’s disease researchers, but recent findings suggest that MANF plays a role in many diseases, also ones with an early childhood-onset. For this reason, it is important to investigate MANF function in different cell types. We have studied how MANF-knockout human embryonic stem cells react to oxidative stress compared to wild-type human embryonic stem cells, by exposing the cells to hydrogen peroxide and ethanol. Results: MANF-knockout human embryonic stem cells were more sensitive to oxidative stress than wild-type cells, but the variation between measurements was remarkable and the differences were statistically insignificant. We found that a transcription factor of our interest localized in the cell nuclei of MANF-knockout cells upon oxidative stress exposure. Such a nuclear translocation did not occur in wild-type cells. Moreover, we found that high concentrations (>2%) of ethanol reduced the viability of cells in only four hours. Discussion: Our findings suggest that MANF-knockout human embryonic stem cells react to oxidative stress differently than wild-type cells. Additional studies are necessary to clarify whether MANF-knockout human embryonic stem cells are indeed more sensitive to oxidative stress than wild-type cells. In the future, it would be interesting to inspect whether MANF protects human embryonic stem cells when the cells are exposed to physiologically relevant ethanol concentrations for longer periods of time.
  • Jakkli, Meera (2020)
    Neural Oscillations at large-scale local and global neural synchrony levels can be detected at the scalp using electroencephalography. This neural activity presents itself in a varied range of frequencies referred to as ‘Brain Waves’. These frequency bands have cognitive significance and have been implicated in several neural functions due to its important role in communicating with functionally-similar but spatially-distinct brain regions. Frontal Asymmetry is the difference in activity between the right and left hemispheres in frontal areas of the brain recorded via EEG and is seen to be a strong indicator of emotional states. Specifically, approach and withdrawal motivation which have been associated with positive and negative emotions respectively. Using a combination of behavioural and physiological methods in measuring preference and responses gives us an accurate representation of the participant responses. In this study, three tests were conducted during a continuous EEG recording. Test 1: The implication of inducing a positive mood before the onset of stimulus line-up and the extent of its effect on emotions and alpha asymmetry is not extensively studied. In this test, we employed the use of an instrumental soundscape for one experimental group before beginning the stimulus presentation to test this effect against a ‘silent’ control group. Test 2: This test aims to compare the participants’ physiological measures (EEG) and behavioural self-reports to audio advertisement stimuli consisting of different categories of music: ‘Brand music’ vs. ‘Campaign’ music or ‘No music’ Controls. Test 3: There is ambiguity in research regarding how frontal alpha asymmetry as measured by EEG and self-report preferences might change with changing the format of the advertisement to: only Audio, Audiovisual and Silent videos. There has been contradictory evidence regarding the impact of music on an individual’s emotions and consequent memory and decision-making. This thesis delves into these questions through the post-study behavioural test and simple binary choice paradigm that measure the above-mentioned in relation with the stimuli presented to participants. Our results did not show a significant difference in frontal asymmetry in the stimulus presentation across the three tests conducted during EEG recording. The behavioural data however indicated significant preference in behavioural self-report ratings for Brand Music- associated stimuli in Test 2 and for Audiovisual advertisement stimuli in Test 3. Results also revealed a significant correlation between ratings given to a stimulus and post-study memorability. The final binary choice paradigm test indicated higher preference to products related to stimulus presentation (‘advertised’ brand) vs similar products not related to the presented stimulus (‘non-advertised’ brand). We anticipate that these results will further help us understand and predict general preferences that can help companies, government policy-makers and the general public be more aware and better equipped to manage their valuable resources of money, time, attention and memory.
  • Uotila, Iiro (2021)
    Evolving societies force universities to transform from the producers of new information sat in their ivory towers towards the role of entrepreneurial universities. The theme of entrepreneurial universities is widely studied internationally, but studies concerning the University of Helsinki (UH) are scarce. The aim of this thesis is to map the current UH bioentrepreneurship ecosystem and the services it provides. The services were mapped and assessed based on how they match the needs of academic bioentrepreneurs. Measures are also suggested on how to develop the ecosystem. This thesis links strongly to the previous literature on entrepreneurial universities and academic entrepreneurship. Entrepreneurial university as a term encompasses an organisation, which strongly supports and encompasses entrepreneurial action in its different functions. Strong technology transfer and commercialization of research via licensing and spinout company formation, is usually linked to entrepreneurial universities. University spinouts are strongly linked to academic entrepreneurship. In spinouts research results and academic tacit knowledge are transformed into enterprises to produce value. The thesis was conducted as a qualitative case study. For the study UH affiliated entities offering entrepreneurship services and bioentrepreneurs originating from within the university were interviewed. The data was analysed with content analysis methods. The results show that UH bioentrepreneurship ecosystem is just in the beginning with multiple useful services but also with some significant flaws. The most significant obstacles preventing the growth of the ecosystem are the university’s negative culture towards entrepreneurship, non-existent communication about the subject and the absence of relevant supportive networks for academic entrepreneurs. Via changing these the critical mass to enable sustainable ecosystem can be achieved.
  • Rooney, Erin Jane (2022)
    Meningeal lymphatic vessels (mLVs), a recent functionally characterized structure in the meninges, contribute to the clearance of macromolecules, immune cells and metabolic waste from the central nervous system to peripheral lymph nodes. Having been identified as a route of clearance, there is a focus on understanding their role in neurological disease pathology. Here we consider their function in the pathology of traumatic brain injury (TBI) particularly in blood solute clearance, lesion progression and neuroinflammatory response. We use a transgenic model of mLV developmental dysfunction, K14-VEGFR3-Ig, to analyze the progression and severity of a controlled cortical impact (CCI) injury. We show that in mice lacking mLVs there are a higher percentage of microglia cells in an activated state in the hippocampus whereas the progression of hematoma and lesion size does not differ from wild type. Our results suggest that at two months post injury, meningeal lymphatics could be functionally important in modulating microglia activation, which is associated with chronic inflammation.
  • Verle, Maarten (2021)
    Advancements in both calcium indicators and optical instrumentation have led to new in vivo techniques, such as Miniscopes, capable of recording the spatiotemporal activity of multiple neurons during unrestrained behaviour in rodents. With these microendoscopic techniques, neuronal populations can be stably recorded over multiple sessions. As a result, Miniscopes allow for the investigation of a brain region’s changing activity patterns as a result of disease progression or behaviour. Recently, open source Miniscope initiatives have led to affordable and accessible versions of this technique. In addition, the collaborative open-source community facilitates rapidly evolving modifications, implementations and designs. Notwithstanding the potential and ever-increasing popularity of Miniscopes, the technique is still in its infancy and not widespread. This study consisted of a background review and a pilot study attempting to image neuronal ensembles in the central nucleus of the amygdala (CeA) using the open-source UCLA V3 Miniscope in mice. Despite not being able to successfully record neuronal activity in the CeA, the study has made progress in generating a protocol for Miniscope implementation at the Pharmacology department of Helsinki. Moreover, the study proposes different adjustments that might be implemented in the future. With the continuation of a synergistic collaboration with the Department of Psychology at the university of Jyväskylä, it is likely that both departments will be able to effectively implement the Miniscope technique in the foreseeable future.
  • Lepistö, Santeri (2023)
    Efficient processing of auditory information begins to emerge early in human ontogeny and establishes foundations for learning language from speech exposure. Here we show that repeated exposure to spoken words causes in neonatal brain attenuated neural responses that are linked to language skills at the age of 24 months. In the study, 75 newborn infants were exposed to repeated presentation of two spoken disyllabic pseudowords. During the word exposure, event-related potentials to presented pseudowords were measured with electroencephalography. The study provides three kinds of findings regarding neonatal brain dynamics and repetitive word exposure. Firstly, the results show that continuous exposure to spoken pseudowords modulates neonatal brain activity and can lead to attenuation of neural responses. This neural suppression likely reflects neonates’ early capacity to recognize spoken words and form neural representations of the stimuli through repetition. Secondly, the attenuated neural responses were bound to the presentation of the first syllable and did not occur after presentation of the second syllable. Thirdly, occurrence of neonatal neural suppression was associated with better expressive language skills later, at the age of 2 years. Altogether, the results provide preliminary evidence that neonatal brain responses to word repetition can be utilized to indicate efficiency of learning language from speech exposure and later state of language development.
  • Kalyanaraman, Shringaa (2024)
    Schizophrenia, a mental disorder affecting over 1% of the world’s population, has a 41-65% chance of being acquired in monozygotic twins, and shows a complex heritable pattern. Research has shown the involvement of various neuronal and glial cell types in the disorder’s progression. Recent studies are focusing on cortical interneurons, as clinical features of schizophrenia such as working memory deficits emerge due to the abnormal activity of these cells . The advent of induced pluripotent stem cell (iPSC) technology has made it easier to study schizophrenia disease mechanisms, with studies revealing differences in morphological and physiological properties of cortical interneurons in patients with schizophrenia. In this thesis , the aim was to optimize iPSC-interneuron differentiation protocol and live-cell imaging method suitable for disease modelling. Interneurons were differentiated from iPSCs with overexpression of inducible transcription factor, Achaete-scute homolog 1 (ASCL1). The iPSCs were derived from twin pairs discordant for schizophrenia and from healthy controls. Expression of interneuron-specific markers was verified using RT-qPCR and validated at the protein level by an immunocytochemistry (ICC) assay in the control cell lines first. Additionally, to estimate the formation of neurites and differences in neurite length and branching, the differentiated interneurons from the controls were subjected to live-cell imaging by IncuCyte S3 live-cell imaging system. Imaging parameters such as cell body cluster filter was optimized to visualize the neurites. To study interneuron involvement in schizophrenia, iPSCs from one twin pair discordant for schizophrenia were successfully differentiated. Interneurons strongly expressed Gamma-aminobutyric acid (GABA) neurotransmitter related neuronal markers: glutamate decarboxylase 67 (GAD67) and GABA at protein level. The neurons were identified as somatostatin (SST) subtype GABAergic neurons by their mRNA and protein expression. While it was possible to observe differences in gene expression, there were no clear differences in the morphology of the differentiated cells as well as the localization of markers in comparison to the healthy controls. Further studies should focus on having a protracted time for differentiation where more mature interneurons can be produced by establishing co-cultures with excitatory neurons. This will help replicate the in vivo cortical machinery which in turn will aid in better understanding of disease mechanisms.