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Browsing by Subject "psychiatric disorders"

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  • Liiwand, Maj Britt (2022)
    Chronic stress has been linked to the pathogenesis of various disorders, such as generalized anxiety disorder, depression, and post-traumatic stress disorder (PTSD). Stress-induced hyperexcitability of the basolateral amygdala (BLA) has implications in anxiety-like behavior. Promising evidence points to the direction of GluK1 subunit containing kainate receptors (KARs) having a role in the modulation of GABAergic transmission in the lateral amygdala (LA). The aim of the present study was to investigate whether dysfunction of KARs contribute to stress-induced amygdala hyperexcitability and anxiogenesis in mice. Chronic restraint stress (CRS) is an animal model simulating chronic psychological stress. An in situ hybridization experiment was performed to investigate how CRS affects expression levels of GluK1 in the different neuronal populations in the LA. These data show that CRS leads to downregulation of GluK1 expression in the parvalbumin-positive (PV+) interneurons specifically. Patch clamp recordings of spontaneous inhibitory postsynaptic currents showed that CRS did not affect synaptic GABAergic transmission to the principal neurons in the LA. Lastly, conditional knock-out (cKO) mice that have the Grik1 gene knocked out selectively in the PV-expressing interneurons showed no change in anxiety-like behavior after CRS while their wild-type counterparts demonstrated an increase in anxiety-like behavior observable in the elevated plus maze test. Thus, ablation of GluK1 in PV+ interneurons affects the stress-induced anxiogenesis. Due to low number of animals, it cannot be confirmed yet whether the deletion leads to stress resilience or a phenotype where even regular handling is an aversive experience comparable to physical restraint. GluK1 KAR modulation of PV+ interneuron excitability and its susceptibility to stress-related alterations is only a recently discovered phenomenon, and even though this study provides some insight into the underlying mechanism, further research is needed. Systematic characterization of the mechanism could provide a novel tool for understanding and treating stress-related pathological anxiety, possibly helping patients suffering from anxiety disorders resistant to current treatments available.
  • Salminen, Annu (2024)
    Functional magnetic resonance imaging (fMRI) has become an important tool in measuring the connectivity of the brain. Based on the connectivity maps acquired from scanning, research is being done for example on how to improve fMRI-guided targeting of transcranial magnetic stimulation (TMS). One of the means is to improve the quality of the imaging. There are some challenges in producing high quality images due to technical limitations and due to patient behavior, most important of which are movement and state of alertness. The aim of this thesis was to find out, if natural viewing during scanning would reduce movement, increase alertness and increase comfortableness of the patients compared to resting state scanning. We had 19 (N=19) patients suffering from treatment resistant MDD (major depressive disorder) scanned to receive fMRIguided TMS -treatment. We divided the fMRI into four sessions: two movie and two resting state sessions. After each session we asked the patients to rate their level of alertness and comfortableness on a visual analogue scale from 0 to 100. We also computed two different movement measures (mean FD [= framewise displacement] Jenkinson and number of FD Power >0.5) of the scanning. We could see a significant difference (p=0.014) in mean FD Jenkinson between movie vs rest indicating that natural viewing reduced movement during scanning. We also could see a significant difference in alertness (p=0.002) between sessions indicating that longer duration of scanning diminishes the state of alertness of the patients. In other parameters we did not see a significant difference between movie and resting state. Our research supports and adds to previous findings that showing a movie during fMRI could reduce movement and that state of alertness could decrease during longer scanning times.
  • Rydgren, Emilie (2018)
    Kainate receptors (KARs) are glutamate receptors that modulate neurotransmission and neuronal excitability. They assemble from five subunits (GRIK1-5 or GluK1-5) present at both pre- and postsynaptic membranes. KAR function is regulated by neuropilin and tolloid-like (NETO) proteins, which also regulate postsynaptic GRIK2 abundance. Some KAR subunit gene variants associate with psychiatric disorders. Moreover, Grik1, Grik2 and Grik4 knock-out (KO) mice display changes in anxiety- and fear-related behaviours. In previous work, Neto2 KO mice expressed higher fear and impaired fear extinction in the fear conditioning paradigm. We hypothesised that this phenotype could be due to reduced KAR subunit abundance in fear-related brain regions, i.e. ventral hippocampus, amygdala and medial prefrontal cortex (mPFC). We specifically investigated GRIK2/3 and GRIK5 levels in the subcellular synaptosomal (SYN) fraction using western blot. We did not observe any difference between genotypes in any of the brain regions. However, our statistical power may have been insufficient, particularly for amygdala and mPFC. Also, an effect on synaptic KAR subunit abundance might be specific to either pre- or postsynaptic compartment, and thus more difficult to detect in SYN fractions. Alternatively, NETO2 absence may affect KAR actions instead of their subunit levels in fear-related brain regions, which could be examined through electrophysiological recordings. Ultimately, unravelling how a molecular system without NETO2 gives rise to fear behaviour in mice may lead to a better understanding of fear-related disorders in human and to new therapeutic strategies.