Browsing by Subject "interaction"
Now showing items 1-3 of 3
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(2019)Classical and rapid-acting antidepressant drugs have been shown to reinstate juvenile-like plasticity in the adult brain, allowing mature neuronal networks to rewire in an environmentally-driven/activity-dependent process. Indeed, antidepressant drugs gradually increase expression of brain-derived neurotrophic factor (BDNF) and can rapidly activate signaling of its high-affinity receptor TRKB. However, the exact mechanism of action underlying drug-induced restoration of juvenile-like plasticity remains poorly understood. In this study we first characterized acute effects of classical and rapid-acting antidepressant drugs on the interaction between TRKB and postsynaptic density (PSD) proteins PSD-93 and PSD-95 in vitro. PSD proteins constitute the core of synaptic complexes by anchoring receptors, ion channels, adhesion proteins and various signaling molecules, and are also involved in protein transport and cell surface localization. PSD proteins have in common their role as key regulators of synaptic structure and function, although PSD-93 and PSD-95 are associated with different functions during development and have opposing effects on the state of plasticity in individual synapses and neurons. Secondly, we investigated changes in mobility of TRKB in dendritic structures in response to treatment with antidepressant drugs in vitro. We found that antidepressant drugs decrease anchoring of TRKB with PSD-93 and PSD-95, and can rapidly increase TRKB turnover in dendritic spines. Our results contribute to the mechanistic model explaining drug-induced restoration of juvenile-like neuronal plasticity, and may provide a common basis for the effects of antidepressant drugs.
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(2023)Knowledge co-production has become more widespread in sustainability research as it possesses the potential as a tool to provide policymakers with usable knowledge in collaboration with researchers to increase the impact of scientific knowledge. This thesis complements the current literature by providing empirical insights of the perception of Finnish national-level policymakers who have participated in Strategic Research Councils (SRC) projects. SRC is a funding instrument with the aim to produce high-quality research with societal impact in collaboration with relevant stakeholders. The perception of Finnish researchers is already somewhat covered in literature and therefore the material for this thesis was collected by interviewing non-researcher participants in SRC projects. The analysis of the material was conducted as a theory-bound qualitative content analysis. The first coding was conducted with a material-based approach to allow the perception of the interviewees to prevail. The final analysis is conducted with three different modes of interaction obtained from the literature: science-push, policy demand, and iterative modes used as main categories. The analysis provides a standpoint on the research question: How do policymakers perceive the interaction in the co-production process? Methods to include policymakers and their participation in national-level co-production processes are versatile in Finland. The knowledge co-production between researchers and national-level policymakers results in usable knowledge and furthers policy uptake especially when collaboration and participation are genuine and profound. This study concludes that the inclusion of policymakers in the early stage of research, two-way communication, iterative interaction, and trust building are factors related to successful interaction, as the policymakers perceive success. The success factors could also help to overcome barriers of co-production presented in earlier literature.
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(2023)Temporal lobe epilepsy (TLE), a condition defined by unprovoked and recurrent seizures originating from the temporal lobe, is among the most ubiquitous of the various forms of epilepsy. Despite being chronic and highly prevalent, the available treatment options concerning the same remains a critical issue. Since the current therapeutic condition of epilepsy requires more development, renewed focus studying its molecular mechanisms and therapies is imminent. One of the longstanding theories trying to decode the molecular perturbations in TLE has been deficits in GABAergic inhibition resulting in abnormal neuronal activation. K+ - Cl- co-transporter (KCC2) activity is vital for maintaining a hyperpolarizing GABA response. The past decades have intimately and causally linked the prognosis of the seizures observed in TLE with deficits in KCC2 functioning. However, the precise mechanisms relevant to the disruption of KCC2 activity are still blurry. Here we show how KCC2 de-stabilization/localization in the neuronal bilayer is a characteristic of epileptic animal tissue. With the help of co-immunoprecipitation assays, western blot, and mass spectrometry, we found that in normal healthy brain tissue, GM1 ganglioside present in the membrane has specific and direct interactions with the KCC2 cotransporter. However, in the pilocarpine model of TLE, the interaction of this complex was significantly disturbed, primarily in the hippocampus and to some extent in the cortex. Our results act as an extension to previous research which stated that the structural association of the KCC2 clusters with neuronal lipid rafts is crucial for the functionality of the KCC2 cotransporter. Having learned about the unique nature of the pathophysiology of TLE, it is imminent to note that additional research in the direction of studying its biochemical pathways is required. The findings of this experimental study support the claim that KCC2 and GM1 as a complex are closely associated in the epileptic conditions and hence, this research paves the way to further explore the role of KCC2 and GM1 as a consequential complex in the pathophysiology of TLE.
Now showing items 1-3 of 3