| 1. |
- Bengtsson, Sara, 1978-, et al.
(författare)
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GABA-A receptor modulating steroids in acute and chronic stress; relevance for cognition and dementia?
- 2020
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Ingår i: Neurobiology of stress. - : Elsevier. - 2352-2895. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive dysfunction, dementia and Alzheimer's disease (AD) are increasing as the population worldwide ages. Therapeutics for these conditions is an unmet need. This review focuses on the role of the positive GABA-A receptor modulating steroid allopregnanolone (APa), it's role in underlying mechanisms for impaired cognition and of AD, and to determine options for therapy of AD. On one hand, APa given intermittently promotes neurogenesis, decreases AD-related pathology and improves cognition. On the other, continuous exposure of APa impairs cognition and deteriorates AD pathology. The disparity between these two outcomes led our groups to analyze the mechanisms underlying the difference. We conclude that the effects of APa depend on administration pattern and that chronic slightly increased APa exposure is harmful to cognitive function and worsens AD pathology whereas single administrations with longer intervals improve cognition and decrease AD pathology. These collaborative assessments provide insights for the therapeutic development of APa and APa antagonists for AD and provide a model for cross laboratory collaborations aimed at generating translatable data for human clinical trials.
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| 2. |
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| 3. |
- Løtvedt, Pia, 1987-, et al.
(författare)
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Chicken domestication changes expression of stress-related genes in brain, pituitary and adrenals
- 2017
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Ingår i: Neurobiology of stress. - : Elsevier. - 2352-2895. ; 7, s. 113-121
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Tidskriftsartikel (refereegranskat)abstract
- Domesticated species have an attenuated behavioral and physiological stress response compared to their wild counterparts, but the genetic mechanisms underlying this change are not fully understood. We investigated gene expression of a panel of stress response-related genes in five tissues known for their involvement in the stress response: hippocampus, hypothalamus, pituitary, adrenal glands and liver of domesticated White Leghorn chickens and compared it with the wild ancestor of all domesticated breeds, the Red Junglefowl. Gene expression was measured both at baseline and after 45 min of restraint stress. Most of the changes in gene expression related to stress were similar to mammals, with an upregulation of genes such as FKBP5, C-FOS and EGR1 in hippocampus and hypothalamus and StAR, MC2R and TH in adrenal glands. We also found a decrease in the expression of CRHR1 in the pituitary of chickens after stress, which could be involved in negative feedback regulation of the stress response. Furthermore, we observed a downregulation of EGR1 and C-FOS in the pituitary following stress, which could be a potential link between stress and its effects on reproduction and growth in chickens. We also found changes in the expression of important genes between breeds such as GR in the hypothalamus, POMC and PC1 in the pituitary and CYP11A1 and HSD3B2 in the adrenal glands. These results suggest that the domesticated White Leghorn may have a higher capacity for negative feedback of the HPA axis, a lower capacity for synthesis of ACTH in the pituitary and a reduced synthesis rate of corticosterone in the adrenal glands compared to Red Junglefowl. All of these findings could explain the attenuated stress response in the domesticated birds.
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| 4. |
- Mayo, Leah, et al.
(författare)
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In the face of stress: Interpreting individual differences in stress-induced facial expressions
- 2019
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Ingår i: NEUROBIOLOGY OF STRESS. - : ELSEVIER SCIENCE INC. - 2352-2895. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Stress is an inevitable part of life that can profoundly impact social and emotional functioning, contributing to the development of psychiatric disease. One key component of emotion and social processing is facial expressions, which humans can readily detect and react to even without conscious awareness. Facial expressions have been the focus of philosophic and scientific interest for centuries. Historically, facial expressions have been relegated to peripheral indices of fixed emotion states. More recently, affective neuroscience has undergone a conceptual revolution, resulting in novel interpretations of these muscle movements. Here, we review the role of facial expressions according to the leading affective neuroscience theories, including constructed emotion and social-motivation accounts. We specifically highlight recent data (Mayo et al, 2018) demonstrating the way in which stress shapes facial expressions and how this is influenced by individual factors. In particular, we focus on the consequence of genetic variation within the endocannabinoid system, a neuromodulatory system implicated in stress and emotion, and its impact on stress-induced facial muscle activity. In a re-analysis of this dataset, we highlight how gender may also influence these processes, conceptualized as variation in the "fight-or-flight" or "tend-and-befriend" behavioral responses to stress. We speculate on how these interpretations may contribute to a broader understanding of facial expressions, discuss the potential use of facial expressions as a trans-diagnostic marker of psychiatric disease, and suggest future work necessary to resolve outstanding questions.
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| 5. |
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| 6. |
- Straus, Laura D., et al.
(författare)
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The role of objective sleep in implicit and explicit affect regulation : A comprehensive review
- 2024
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Ingår i: Neurobiology of Stress. - : Elsevier. - 2352-2895. ; 31
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Forskningsöversikt (refereegranskat)abstract
- Impairments in sleep and affect regulation are evident across a wide range of mental disorders. Understanding the sleep factors that relate to affect regulatory difficulties will inform mechanistic understanding and aid in treatment. Despite rising interest, some research challenges in this area include integrating across different clinical and non-clinical literatures investigating the role of sleep architecture (measured with polysomnography) and experimentally manipulated sleep, as well as integrating more explicit versus implicit affect regulation processes. In this comprehensive review, we use a unifying framework to examine sleep's relationship with implicit-automatic regulation and explicit-controlled regulation, both of which are relevant to mental health (e.g., PTSD and depression). Many studies of implicit-automatic regulation (e.g., fear extinction and safety learning) demonstrate the importance of sleep, and REM sleep specifically. Studies of explicit-controlled regulation (e.g., cognitive reappraisal and expressive suppression) are less consistent in their findings, with results differing depending on the type of affect regulation and/or way that sleep was measured or manipulated. There is a clear relationship between objective sleep and affect regulation processes. However, there is a need for 1) more studies focusing on sleep and explicit-controlled affect regulation; 2) replication with the same types of regulation strategies; 3) more studies experimentally manipulating sleep to examine its impact on affect regulation and vice versa in order to infer cause and effect; and 4) more studies looking at sleep's impact on next-day affect regulation (not just overnight change in affect reactivity).
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| 7. |
- Svensson, Martina, et al.
(författare)
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Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia
- 2016
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Ingår i: Neurobiology of Stress. - : Elsevier BV. - 2352-2895. ; 5, s. 8-18
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise is known to be a beneficial factor by increasing the cellular stress tolerance. In ischemic stroke, physical exercise is suggested to both limit the brain injury and facilitate behavioral recovery. In this study we investigated the effect of physical exercise on brain damage following global cerebral ischemia in mice. We aimed to study the effects of 4.5 weeks of forced treadmill running prior to ischemia on neuronal damage, neuroinflammation and its effect on general stress by measuring corticosterone in feces. We subjected C57bl/6 mice (n = 63) to either treadmill running or a sedentary program prior to induction of global ischemia. Anxious, depressive, and cognitive behaviors were analyzed. Stress levels were analyzed using a corticosterone ELISA. Inflammatory and neurological outcomes were analyzed using immunohistochemistry, multiplex electrochemoluminescence ELISA and Western blot. To our surprise, we found that forced treadmill running induced a stress response, with increased anxiety in the Open Field test and increased levels of corticosterone. In accordance, mice subjected to forced exercise prior to ischemia developed larger neuronal damage in the hippocampus and showed higher cytokine levels in the brain and blood compared to non-exercised mice. The extent of neuronal damage correlated with increased corticosterone levels. To compare forced treadmill with voluntary wheel running, we used a different set of mice that exercised freely on running wheels. These mice did not show any anxiety or increased corticosterone levels. Altogether, our results indicate that exercise pre-conditioning may not be beneficial if the animals are forced to run as it can induce a detrimental stress response.
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| 8. |
- Tanelian, Arax, et al.
(författare)
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Resilience or susceptibility to traumatic stress : Potential influence of the microbiome
- 2022
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Ingår i: Neurobiology of Stress. - : Elsevier BV. - 2352-2895. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to traumatic stress is a major risk factor for development of neuropsychiatric disorders in a sub-population of individuals, while others remain resilient. The mechanisms and contributing factors differentiating between these phenotypes are still unclear. We hypothesize that inter-individual differences in the microbial composition and function contribute to host resilience or susceptibility to stress-induced psychopathologies. The current study aimed to characterize gut microbial community before and after exposure to traumatic stress in an animal model of PTSD. Sprague-Dawley male rats were randomly divided into unstressed controls and experimental group subjected to Single Prolonged Stress (SPS). After 14 days, behavioral analyses were performed using Open Field, Social Interaction and Elevated Plus Maze tests. Based on the anxiety measures, the SPS group was further subdivided into resilient (SPS-R) and susceptible (SPS–S) cohorts. The animals were sacrificed after the last behavioral test and cecum, colon, hippocampus, and medial prefrontal cortex were dissected. Prior to SPS and immediately after Open Field test, fecal samples were collected from each rat for 16S V3–V4 ribosomal DNA sequencing, whereas urine samples were collected before SPS, 90 min into immobilization and on the day of sacrifice to measure epinephrine and norepinephrine levels. Analyses of the fecal microbiota revealed significant differences in microbial communities and in their predictive functionality among the groups before and after SPS stressors. Before SPS, the SPS-S subgroup harbored microbiota with an overall pro-inflammatory phenotype, whereas SPS-R subgroup had microbiota with an overall anti-inflammatory phenotype, with predictive functional pathways enriched in carbohydrate and lipid metabolism and decreased in amino acid metabolism and neurodegenerative diseases. After SPS, the gut microbial communities and their predictive functionality shifted especially in SPS cohorts, with volatility at the genus level correlating inversely with Anxiety Index. In line with the alterations seen in the gut microbiota, the levels of cecal short chain fatty acids were also altered, with SPS-S subgroup having significantly lower levels of acetate, valerate and caproate. The levels of acetate inversely correlated with Anxiety Index. Interestingly, urinary epinephrine and norepinephrine levels were also higher in the SPS-S subgroup at baseline and during stress, indicative of an altered sympathoadrenal stress axis. Finally, shorter colon (marker of intestinal inflammation) and a lower claudin-5 protein expression (marker for increased blood brain barrier permeability) were observed in the SPS-S subgroup. Taken together, our results suggest microbiota is a potential factor in predisposing subjects either to stress susceptibility or resilience. Moreover, SPS triggered significant shifts in the gut microbiota, their metabolites and brain permeability. These findings could lead to new therapeutic directions for PTSD possibly through the controlled manipulation of gut microbiota. It may enable early identification of individuals more likely to develop prolonged anxiogenic symptoms following traumatic stress.
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| 9. |
- Treccani, Giulia, et al.
(författare)
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Early life adversity targets the transcriptional signature of hippocampal NG2+ glia and affects voltage gated sodium (Nav) channels properties
- 2021
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Ingår i: Neurobiology of Stress. - : Elsevier BV. - 2352-2895. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells. First, we have established a link between maternal behavior, activation of the offspring's stress response and heterogeneity in the outcome to LBN manipulation. We further showed that LBN targets the hippocampal NG2+ transcriptome with glucocorticoids being an important mediator of the LBN-induced molecular changes. LBN altered the NG2+ transcriptome and these transcriptional effects were correlated with glucocorticoids levels. The functional relevance of one LBN-induced candidate gene, Scn7a, could be confirmed by an increase in the density of voltage-gated sodium (Nav) channel activated currents in hippocampal NG2+ cells. Scn7a remained upregulated until adulthood in LBN animals, which displayed impaired cognitive performance. Considering that Nav channels are important for NG2+ cell-to-neuron communication, our findings provide novel insights into the disruption of this process in LBN mice.
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