Browsing by Subject "anxiety"

Chronic psychosocial stress is a major risk factor for anxiety disorders, but the molecular background is still poorly known. Chronic social defeat stress (CSDS) is a mouse model simulating the psychosocial stress that humans face in their life. In CSDS, the examined mice are confronted by an aggressor mouse daily for 10 days, leading to defeat behavior and predisposing to anxiety-like symptoms. Some individuals develop these symptoms (susceptible) whereas others do not (resilient). Chronic stress has been shown to alter myelin-related gene transcription and myelin microstructure. Myelin is a membranous component around axons increasing the velocity of action potentials, and it is produced by oligodendrocytes (OLs). In this study, I investigated if CSDS affects the number of OLs or the size of the myelinated area (estimating the amount of myelin) in two inbred mouse strains that differ in their innate level of anxiety: the non-anxious C57BL/6NCrl (B6) and anxious DBA/2NCrl (D2). I studied three brain regions previously associated with anxiety: the medial prefrontal cortex (mPFC), bed nucleus of stria terminalis (BNST) and ventral hippocampus (vHP). The mice used in this study were previously exposed to CSDS and divided into resilient or susceptible phenotypes, and their brains were collected together with control mice. I performed two immunohistochemical staining experiments to calculate the number of OLs and to measure the myelinated area. I used anti-CNPase for OL cell counts and BlackGold II to stain myelin. I manually calculated the number of OLs using CNPase and cell morphology as markers. I built a macro to measure the BlackGold II stained myelinated area. I also measured the thickness of the corpus callosum (CC, major white matter tract) using the CNPase stained images to examine if the thickness is affected by CSDS. I observed a strain and region-specific effect of chronic stress in the BNST; B6 resilient mice had more OLs than susceptible mice whereas no differences were seen in the D2 strain, or other B6 brain regions. The size of the myelinated area did not differ between the phenotypes in either strain. Moreover, there was no significant correlation between the myelinated area and OL cell number. The CC thickness did not differ between the phenotypes. My findings indicate that myelin and OLs are affected by stress in a region specific manner and possibly contribute to the stress-resilient behavior. The response is genetic background-dependent, as I saw differences in B6 mice but not in D2 mice. Because CC thickness did not differ between the phenotypes, we suggest that CSDS does not induce extensive white matter atrophy in the mice brain. The mechanism underlying this dynamic myelin plasticity during stress requires more investigation, but this study provides evidence that alterations in OLs associate with chronic stress.

The bed nucleus of the stria terminalis (BNST) is currently widely studied due to its impact in the anxiety-, stress-, and fearrelated behaviours, as well as in addiction. The BNST is highly heterogeneous brain area constituting of set of subnuclei and a variety of neuron populations, properties of which have only partially been revealed by the earlier research. One of the neuron populations, on which only a very little research has been conducted, is the somatostatin (Sst) expressing neurons, highly abundant in the anterodorsal part of the BNST (adBNST), especially in oval and juxtacapsular nuclei of the BNST. This work aims to elucidate the connectivity of this Sst-neuron population, and their role in the behaviours related to BNST activation, particularly the anxiety-, reward-, and drug withdrawal-related behaviours. To specifically study the somatostatin neuron population in the adBNST, I targeted the neurons using stereotaxic delivery of AAV-vectors encoding a myristylated green fluorescent protein (GFP) for neuronal tracing to Sst-Cre-tdTomato reporter line mice (n=2), and Cre-inducible hM3Dq-DREADDs to Sst-IRES-Cre mice (n=21), with Cre-inducible mCherry fluorescent protein as a control (n=20). The mice were treated with activation-inducing 1.0 mg/kg i.p. clozapine-N-oxide (CNO) 30 min prior to the behavioural tests. To assess acute anxiety-like behaviour, I used the elevated-plus maze paradigm and a modified open field test, in which a novel object is introduced to the arena in the middle of the trial. To study the potential effect on reward-associated behaviours, I used the biased conditioned place preference (CPP) test, and for the withdrawal-linked behaviours, we used a method to precipitate the withdrawal symptoms with naltrexone in subchronically morphine-treated mice (n=9 hM3Dq, n=8 control). The neuronal tracing revealed that the adBNST Sst-neurons project to areas known to partake in stress and fear reactions as well as in autonomic and homeostatic control. Namely, projections were seen in medial and central amygdaloidal nuclei, lateral hypothalamus, periaqueductal grey, ventral pallidum, and parabrachial nucleus. In the elevated-plus maze, the CNO-induced activation of the Sst-neurons did not have any effect on the locomotor activity of the mice between the groups. At the same time, Sst activation did not seem to have any significant effect on the time the mice spent in the open arms, nor in the exploratory activities, like the frequency of the head dips or the stretch-attend postures. In line with these results, no effect on the movement between the groups was observed in the open field test. Similarly, no differences in anxiety-related behaviours, like in the time spent in the centre of the arena or in the number of contacts with the novel object during the last phase of the test, were observed. The CPP test failed to show any meaningful rewarding or aversive properties of CNO-induced activation of the Sst-neurons, while the movement rates of the groups during the conditioning trials were not different in statistically significant way. As for the withdrawal symptoms, all the mice showed the predetermined symptoms, but the test failed to show any differences between the study groups. The neuronal tracing revealed connectivity for the adBNST Sst-neurons with brain regions involved in fear- and anxiety behaviour, social encounters, and autonomic control. In spite of this, the CNO-induced chemogenetic activation of the adBNST Sst-neurons failed to show any significant behavioural effects in the chosen paradigms for anxiety-, and reward-related behaviours, and for withdrawal symptoms. Further research is needed to dissect the Sst-subcircuitry of adBNST, both in order to verify the observed output regions, and to elucidate the role these neurons play in modification of behavioural phenotypes.

Background: We studied two different visual effects: In brightness induction, the perceived brightness of the stimulus is altered by the luminance of its surround, and in orientation selective contrast suppression the contrast of the stimulus appears lower when surrounded by a collinear surround of higher contrast. In previous studies, orientation selective contrast suppression has been found to be altered in patients who have been diagnosed with depression. Objectives: We measured symptoms of anxiety and depression in our non-clinical sample in order to compare them to their performance in the visual experiments. The goal of our online experiment was also to replicate both of the visual effects without a tightly controlled environment. Methods: Our online experiment consisted of a repeated measures design, with separate blocks for randomised brightness trials, randomised contrast trials, and self-report mental health questionnaires. In the visual trials participants were asked to estimate the brightness or contrast level of a central stimulus, while its surround was varied in luminance or contrast. Our sample consisted of 76 healthy participants with a mean age of 25. Results and conclusions: We managed to replicate both the brightness induction and the orientation selective contrast suppression effects, and found that the use of different electronic devices in completion of the study had no significant effect on the results. Participants reported varying levels of symptoms of anxiety and depression, and 61.6 % of them crossed clinically relevant cut-off points. We did not find a statistically significant connection between the visual effects and symptoms of anxiety and depression. This is encouraging, as it indicates that having only a few symptoms of mental disorders does not alter contrast perception. However, finding out at what point is the contrast perception altered, warrants further study.

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.

Sikiöseulonta on Suomessa osa kuntien tarjoamaa julkista terveydenhuoltoa. Seulontoja ohjaa Valtioneuvoston asettama seulonta-asetus. Osallistuminen on ilmaista ja vapaaehtoista. Tavoitteena on löytää rakenteellisia ja kromosomaalisia poikkeavuuksia ensimmäisen ja toisen raskauskolmanneksen aikana. Alkuraskauden aikana naisille annetaan sekä kirjallista että suullista tietoa seulonnan tavoitteista, rajoitteista ja menetelmistä, minkä jälkeen heidän tulee tehdä itsenäinen, tietoon pohjautuva päätös osallistumisestaan. Useat tutkimukset ovat kuitenkin osoittaneet, että seulontoihin osallistuvat naiset ovat tyytymättömiä terveydenhuollosta saaneensa tiedon määrään ja selkeyteen. Selvitimme tutkimuksessamme Helsingin alueella seulontoihin osallistuneiden naisten tyytyväisyyttä tiedonantoon ja tietämystä seulonnoista. Tutkimusaineisto kerättiin kyselykaavakkeilla, joita tarjottiin jokaiselle Helsingin yliopistollisessa keskussairaalassa seulontaan osallistuneelle. Kyselyyn vastaaminen oli vapaaehtoista. Tutkimuksessa huomioitiin vastaukset kaavakkeissa, jotka oli täytetty heti seulontapositiivisen löydöksen kuulemisen jälkeen ja jatkotutkimusten aikana. Kyselyyn vastasi 168 naista. Tuloksemme osoittavat, että Naistenklinikalla saatu tiedonanto koettiin merkittävästi aiempien seulontavastaanottojen neuvontaa selkeämmäksi ja perusteellisemmaksi. Valtaosa naisista (73%) olivat jatkotutkimuksia edeltävästi huolissaan, mutta alle puolet vastaajista (47,4%) olivat miettineet arvojaan tutkimuksia edeltävästi. Puolet (53,2%) uskoivat raskautta koskevan huolestuneisuutensa jatkuvan, vaikka jatkotutkimuksien tulos osoittautuisi normaaliksi. Suurin osa (82,4%) naisista olivat tietoisia jatkotutkimusten vapaaehtoisuudesta ja tyytyväisiä päätökseensä osallistua (86%). Seulontapositiivisen tuloksen saamisen jälkeen naisille jää siis epätietoinen olo, johon liittyy ahdistuneisuutta ja hämmennystä. Tämän olotilan välttämiseksi tarvitaankin korkealaatuista neuvontaa heti ensimmäiseltä vastaanottokäynniltä lähtien. Vanhempien oikeanlainen, riittävän kattava neuvonta on myös tärkeää, jotta sikiöseulonnoissa oleellisen tietoon pohjautuvan päätöksen tekeminen on mahdollista.