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61.
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62.
  • Das, Roshni, et al. (författare)
  • Medroxyprogesterone acetate positively modulates specific GABAA-receptor subtypes - affecting memory and cognition
  • 2022
  • Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 141
  • Tidskriftsartikel (refereegranskat)abstract
    • Medroxyprogesterone acetate (MPA) is a progestin widely used in humans as hormone replacement therapy and at other indications. Many progestin metabolites, as the progesterone metabolite allopregnanolone, have GABAA-receptor modulatory effects and are known to affect memory, learning, appetite, and mood. In women, 4 years chronic treatment with MPA doubles the frequency of dementia and in rats, MPA causes cognitive impairment related to the GABAergic system. Activation of the membrane bound GABAA receptor results in a chloride ion flux that can be studied by whole-cell patch-clamp electrophysiological recordings. The purpose of this study was to clarify the modulatory effects of MPA and specific MPA metabolites, with structures like known GABAA-receptor modulators, on different GABAA-receptor subtypes. An additional aim was to verify the results as steroid effects on GABA response in single cells taken from rat hypothalamus. HEK-293 cell-lines permanently expressing the recombinant human GABAA-receptor subtype α1β2γ2L or α5β3γ2L or α2β3γ2S were created. The MPA metabolites 3α5α-MPA,3β5α-MPA and 3β5β-MPA were synthesised and purified for electrophysiological patch-clamp measurements with a Dynaflow system. The effects of MPA and tetrahydrodeoxycorticosterone were also studied. None of the studied MPA metabolites affected the responses mediated by α1β2γ2L or α5β3γ2L GABAA receptors. Contrary, MPA clearly acted both as a positive modulator and as a direct activator of the α5β3γ2L and α2β3γ2S GABAA receptors. However, in concentrations up to 10 μM, MPA was inactive at the α1β2γ2L GABAA receptor. In the patch-clamp recordings from dissociated cells of the preoptic area in rats, MPA increased the amplitude of responses to GABA. In addition, MPA alone without added GABA, evoked a current response. In conclusion, MPA acts as a positive modulator of specific GABAA receptor subtypes expressed in HEK cells and at native GABA receptors in single cells from the hypothalamic preoptic area.
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63.
  • Derntl, Birgit, et al. (författare)
  • Estradiol modulates changes in effective connectivity in emotion regulation networks
  • 2024
  • Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 167
  • Tidskriftsartikel (refereegranskat)abstract
    • Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So far, the neural underpinnings of the effect of E2 on emotional experience have been investigated using task-based functional magnetic resonance imaging (fMRI) and functional connectivity. In the present study, we examined whether the intrinsic network dynamics at rest (i. e., directed effective connectivity) related to emotion regulation are (1) modulated by E2 levels and (2) linked to behavioral emotion regulation ability. Hence, 29 naturally cycling women participated in two resting-state fMRI scans in their early follicular phase after being administered a placebo or an E2 valerate, respectively. Emotion regulation ability was assessed using a standard emotion regulation task in which participants were asked to down-regulate their emotions in response to negative images. The regions of two functionally predefined neural networks related to emotional down-regulation and reactivity were used to investigate effective connectivity at rest using spectral dynamic causal modelling. We found that E2, compared to placebo, resulted in changes in effective connectivity in both networks. In the regulation network, prefrontal regions showed distinct connectivity in the E2 compared to the placebo condition, while mixed results evolved in the emotional reactivity network. Stepwise regressions revealed that in the E2 condition a connection from the parietal to the prefrontal cortex predicted regulation ability. Our results demonstrate that E2 levels influence effective connectivity in networks underlying emotion regulation and emotional reactivity. Thus, E2 and its potential modification via hormonal administration may play a supporting role in the treatment of mental disorders that show a dysregulation of emotions.
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64.
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65.
  • Ebner, Natalie C., et al. (författare)
  • Oxytocin’s effect on resting-state functional connectivity varies by age and sex
  • 2016
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 69, s. 50-59
  • Tidskriftsartikel (refereegranskat)abstract
    • The neuropeptide oxytocin plays a role in social cognition and affective processing. The neural processes underlying these effects are not well understood. Modulation of connectivity strength between subcortical and cortical regions has been suggested as one possible mechanism. The current study investigated effects of intranasal oxytocin administration on resting-state functional connectivity between amygdala and medial prefrontal cortex (mPFC), as two regions involved in social-cognitive and affective processing. Going beyond previous work that largely examined young male participants, our study comprised young and older men and women to identify age and sex variations in oxytocin’s central processes. This approach was based on known hormonal differences among these groups and emerging evidence of sex differences in oxytocin’s effects on amygdala reactivity and age-by-sex-modulated effects of oxytocin in affective processing. In a double-blind design, 79 participants were randomly assigned to self-administer either intranasal oxytocin or placebo before undergoing resting-state functional magnetic resonance imaging. Using a targeted region-to-region approach, resting-state functional connectivity strength between bilateral amygdala and mPFC was examined. Participants in the oxytocin compared to the placebo group and men compared to women had overall greater amygdala–mPFC connectivity strength at rest. These main effects were qualified by a significant three-way interaction: while oxytocin compared to placebo administration increased resting-state amygdala–mPFC connectivity for young women, oxytocin did not significantly influence connectivity in the other age-by-sex subgroups. This study provides novel evidence of age-by-sex differences in how oxytocin modulates resting-state brain connectivity, furthering our understanding of how oxytocin affects brain networks at rest.
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66.
  • Edvinsson, Åsa, 1982-, et al. (författare)
  • Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction
  • 2017
  • Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 80, s. 15-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.Methods: 160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.Results: Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p = 0.000001, macrophage colony-stimulating factor 1 (CSF-1), p = 0.000004, and fractalkine (CX3CL1), p =0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p = 0.000011, vascular endothelial growth factor A (VEGF-A), p =0.000016, and IL-15 receptor subunit alpha (IL-15RA), p = 0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.Conclusion: Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.
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67.
  • Eek, Frida, et al. (författare)
  • Cortisol, sleep, and recovery: some gender differences but no straight associations
  • 2012
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 37:1, s. 176-184
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract in UndeterminedBACKGROUND: Work related fatigue has been suggested as a link in the assumed sequence of events between repeated adverse work demands and the development of work related stress, which may be associated with changes in concentrations of cortisol, psychological overload and, in the long run, health problems. Insufficient sleep is a contributing factor to lack of recovery, but previous studies on associations between subjective aspects of sleep and recovery, and cortisol, have been inconclusive. The aim with the present study was to examine possible associations between cortisol measures and (I) self-rated recovery, (II) occupational fatigue and (III) subjective sleep quality the night preceding cortisol sampling. Further, possible gender differences were tested. METHODS: Salivary cortisol was measured in 581 persons during a working day, at awakening, +30min and in the evening. Various measures of subjective sleep and recovery were analyzed in relation to cortisol. RESULTS: Few correlations between cortisol and any sleep- or recovery parameters were found. However, some significant associations were found between cortisol and a few measures of more chronic aspects of sleep and recovery. Gender stratified analyses showed somewhat differing associations among men and women. This indicates that possible associations and pathways between lack of recovery/sleepiness and cortisol, and in the long run, unhealth, may not be similar for men and women.
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68.
  • Egecioglu, Emil, 1977, et al. (författare)
  • The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents
  • 2013
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:8, s. 1259-1270
  • Tidskriftsartikel (refereegranskat)abstract
    • Development of alcohol use disorders largely depends on the effects of alcohol on the brain reward systems. Emerging evidence indicate that common mechanisms regulate food and alcohol intake and raise the possibility that endocrine signals from the gut may play an important role for alcohol consumption, alcohol-induced reward and the motivation to consume alcohol. Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide regulating food intake and glucose homeostasis, has recently been shown to target central brain areas involved in reward and motivation, including the ventral tegmental area and nucleus accumbens. Herein we investigated the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on various measures of alcohol-induced reward as well as on alcohol intake and alcohol seeking behavior in rodents. Treatment with Ex4, at a dose with no effect per se, attenuated alcohol-induced locomotor stimulation and accumbal dopamine release in mice. Furthermore, conditioned place preference for alcohol was abolished by both acute and chronic treatment with Ex4 in mice. Finally we found that Ex4 treatment decreased alcohol intake, using the intermittent access 20% alcohol two-bottle-choice model, as well as alcohol seeking behavior, using the progressive ratio test in the operant self-administration model, in rats. These novel findings indicate that GLP-1 signaling attenuates the reinforcing properties of alcohol implying that the physiological role of GLP-1 extends beyond glucose homeostasis and food intake regulation. Collectively these findings implicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for alcohol use disorders.
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69.
  • Ehlert, Ulrike, et al. (författare)
  • Sexual steroids during the course of female life
  • 2019
  • Ingår i: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 107, s. 67-67
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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70.
  • Ellingsen, Dan-Mikael, 1985, et al. (författare)
  • In touch with your emotions: Oxytocin and touch change social impressions while others' facial expressions can alter touch
  • 2014
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 39, s. 11-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Interpersonal touch is frequently used for communicating emotions, strengthen social bonds and to give others pleasure. The neuropeptide oxytocin increases social interest, improves recognition of others' emotions, and it is released during touch. Here, we investigated how oxytocin and gentle human touch affect social impressions of others, and vice versa, how others' facial expressions and oxytocin affect touch experience. In a placebo-controlled crossover study using intranasal oxytocin, 40 healthy volunteers viewed faces with different facial expressions along with concomitant gentle human touch or control machine touch, while pupil diameter was monitored. After each stimulus pair, participants rated the perceived friendliness and attractiveness of the faces, perceived facial expression, or pleasantness and intensity of the touch. After intranasal oxytocin treatment, gentle human touch had a sharpening effect on social evaluations of others relative to machine touch, such that frowning faces were rated as less friendly and attractive, whereas smiling faces were rated as more friendly and attractive. Conversely, smiling faces increased, whereas frowning faces reduced, pleasantness of concomitant touch the latter effect being stronger for human touch. Oxytocin did not alter touch pleasantness. Pupillary responses, a measure of attentional allocation, were larger to human touch than to equally intense machine touch, especially when paired with a smiling face. Overall, our results point to mechanisms important for human affiliation and social bond formation. (C) 2013 Elsevier Ltd. All rights reserved.
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