| 1. |
- Nätt, Daniel, 1980-, et al.
(författare)
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Large Sex Differences in Chicken Behavior and Brain Gene Expression Coincide with Few Differences in Promoter DNA-Methylation
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:4, s. e96376-
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Tidskriftsartikel (refereegranskat)abstract
- While behavioral sex differences have repeatedly been reported across taxa, the underlying epigenetic mechanisms in thebrain are mostly lacking. Birds have previously shown to have only limited dosage compensation, leading to high sex bias ofZ-chromosome gene expression. In chickens, a male hyper-methylated region (MHM) on the Z-chromosome has beenassociated with a local type of dosage compensation, but a more detailed characterization of the avian methylome islimiting our interpretations. Here we report an analysis of genome wide sex differences in promoter DNA-methylation andgene expression in the brain of three weeks old chickens, and associated sex differences in behavior of Red Junglefowl(ancestor of domestic chickens). Combining DNA-methylation tiling arrays with gene expression microarrays we show that aspecific locus of the MHM region, together with the promoter for the zinc finger RNA binding protein (ZFR) gene onchromosome 1, is strongly associated with sex dimorphism in gene expression. Except for this, we found few differences inpromoter DNA-methylation, even though hundreds of genes were robustly differentially expressed across distantly relatedbreeds. Several of the differentially expressed genes are known to affect behavior, and as suggested from their functionalannotation, we found that female Red Junglefowl are more explorative and fearful in a range of tests performed throughouttheir lives. This paper identifies new sites and, with increased resolution, confirms known sites where DNA-methylationseems to affect sexually dimorphic gene expression, but the general lack of this association is noticeable and strengthensthe view that birds do not have dosage compensation.
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| 2. |
- Jöngren, Markus, 1981-, et al.
(författare)
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Brain gene expression in relation to fearfulness in female red junglefowl (Gallus gallus)
- 2010
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Ingår i: Genes, Brain and Behavior. - : International and Neural genetics Society. - 1601-1848 .- 1601-183X. ; 9:7, s. 751-758
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Tidskriftsartikel (refereegranskat)abstract
- The biology of fear is central to animal welfare and hasbeen a major target for selection during domestication.Fear responses were studied in female red junglefowl(RJF), the ancestor of domesticated chickens. A totalof 31 females were tested in a ground predator test,an aerial predator test and a tonic immobility (TI)test, in order to assess their level of fearfulnessacross different situations. Two to six variables fromeach test were entered into a principal component(PC) analysis, which showed one major fearfulnesscomponent (explaining 27% of the variance). Based onthe PC scores, four high- and four low-fearful birds werethen selected for gene expression analysis. From eachof these birds, the midbrain region (including thalamus,hypothalamus, pituitary, mesencephalon, pons, nucleustractus solitarii and medulla oblongata), was collectedand global gene expression compared between groupsusing a 14k chicken cDNA microarray. There were 13significantly differentially expressed (DE) genes (basedonM > 1 andB > 0; FDR-adjusted P < 0.05) between thefearful and non-fearful females. Among the DE genes,we identified the neuroprotein Axin1, two potentialDNA/RNA regulating proteins and a retrotransposontranscript situated in a well-studied quantitative traitloci (QTL) region on chromosome 1, known to affectseveral domestication-related traits. The differentiallyexpressed genes may be part of a possible molecularmechanism controlling fear responses in fowl.
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| 3. |
- Lindqvist, Christina, et al.
(författare)
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Transmission of Stress-Induced Learning Impairment and Associated Brain Gene Expression from Parents to Offspring in Chickens
- 2007
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:4, s. e364-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stress influences many aspects of animal behaviour and is a major factor driving populations to adapt to changing living conditions, such as during domestication. Stress can affect offspring through non-genetic mechanisms, but recent research indicates that inherited epigenetic modifications of the genome could possibly also be involved. Methodology/Principal Findings: Red junglefowl (RJF, ancestors of modern chickens) and domesticated White Leghorn (WL) chickens were raised in a stressful environment (unpredictable light-dark rhythm) and control animals in similar pens, but on a 12/12 h light-dark rhythm. WL in both treatments had poorer spatial learning ability than RJF, and in both populations, stress caused a reduced ability to solve a spatial learning task. Offspring of stressed WL, but not RJF, raised without parental contact, had a reduced spatial learning ability compared to offspring of non-stressed animals in a similar test as that used for their parents. Offspring of stressed WL were also more competitive and grew faster than offspring of non-stressed parents. Using a whole-genome cDNA microarray, we found that in WL, the same changes in hypothalamic gene expression profile caused by stress in the parents were also found in the offspring. In offspring of stressed WL, at least 31 genes were up- or down-regulated in the hypothalamus and pituitary compared to offspring of non-stressed parents. Conclusions/ Significance: Our results suggest that, in WL the gene expression response to stress, as well as some behavioural stress responses, were transmitted across generations. The ability to transmit epigenetic information and behaviour modifications between generations may therefore have been favoured by domestication. The mechanisms involved remain to be investigated; epigenetic modifications could either have been inherited or acquired de novo in the specific egg environment. In both cases, this would offer a novel explanation to rapid evolutionary adaptation of a population.
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| 4. |
- Mayo, Leah M., 1987-, et al.
(författare)
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Protective effects of elevated anandamide on stress and fear-related behaviors : translational evidence from humans and mice
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:5, s. 993-1005
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Tidskriftsartikel (refereegranskat)abstract
- Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C-greater thanA substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.
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| 5. |
- Nätt, Daniel, 1980-, et al.
(författare)
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Plumage color and feather pecking--behavioral differences associated with PMEL17 genotypes in chicken (Gallus gallus)
- 2007
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Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 37:2, s. 399-407
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Tidskriftsartikel (refereegranskat)abstract
- An F 5 generation of an advanced inter-cross between red junglefowl (wild-type) and White Leghorn (domesticated) was used to investigate earlier findings suggesting that a mutation in the plumage color gene PMEL17 protects against victimization to feather pecking (FP). F 4 parents were selected according to genotype to produce PMEL17 homozygous offspring (i/i and I/I respectively). Birds were raised and their behavior recorded in groups of either two wild-type i/i (dark colored) and one white I/I, or two I/I and one i/i. In addition each bird was tested for feather preference, reaction to novelty, open-field activity, fear for humans, and tonic-immobility. In the home-pens, i/i birds were more feather pecked and had poorer feather condition than I/I birds. No pecking preference for immobile dark colored feathers was observed. In the open-field test i/i birds vocalized more and earlier than I/I birds, and in the fear-for-human test I/I birds had higher activity at 21 weeks of age. No other behavior differences were observed, but clearly, genotypes of PMEL17 affected some aspects of behavior. Such behavioral differences might be important aspects of the mechanism which predispose i/i individuals for being victims of FP.
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| 6. |
- Nätt, Daniel, 1980-
(författare)
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Stress and the Offspring : Adaptive Transgenerational Effects of Unpredictability on Behaviour and Gene Expression in Chickens (Gallus gallus)
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Environmental stress has shown to affect both the exposed individuals and the development of their offspring. Generally, it is thought that the stressed organism responds to stress by trying to adapt to it. This thesis investigates possible evolutionary consequences of cross-generational transmissions of stress, where the parent has been stressed but the offspring has not. In two studies we have exposed chicken parents of different breeds to an unpredictable circadian light rhythm, to investigate the influence of genetic background on the transmission of behaviour and patterns of genome-wide gene expression across generations. In Paper I, we can show that the domesticated chicken, by means of epigenetic factors, transmit their behaviours as well as their gene expression profiles to their offspring to a higher extent than their wild ancestor, the red junglefowl. Furthermore, in Paper II, even though the offspring never experienced the stress or had any contact with their stressed parents, they seemed to have adapted to it, which suggests that the parents might have prepared (or pre-adapted) them for living in the unpredictable environment. Additionally, eggs of stressed hens showed increased levels of estradiol that might have affected gene expression of specific immune genes, which were up-regulated in the offspring of stressed parents. It is possible that the traditional distinction between stress responses and evolutionary adaptation may be reevaluated, since our results indicate that they could be parts of the same evolutionary event.
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| 7. |
- Nätt, Daniel, 1980-, et al.
(författare)
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Transgenerational Phenotypic Tuning of Offspring : Adaptive Responses to a Prenatal Environmental Challenge in Chickens
- 2008
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Stress may affect both the exposed individuals and the development of their offspring. We have previously shown that offspring of stressed domestic chickens can inherit the stressed-induced learning impairments of their parents and the associated modifications in brain gene expression. In this study we investigated possible adaptive aspects of such cross-generation transmissions. We hypothesized that stress would cause chickens to show a more conservative feeding strategy and to be more dominant, and that these adaptations would be transmitted to the offspring. Parents were raised in an unpredictable diurnal light rhythm (stress treatment) or in control conditions (12:12 h light:dark). In a foraging test, stressed birds pecked more at freely available than at hidden and more attractive food compared to birds from the control group. Female offspring of stressed birds, raised in control conditions without parental contact, showed a similar foraging behavior, differing from offspring of control birds. Furthermore, adult offspring of stressed birds performed more food pecks in a dominance test, showed a higher preference for high energy food, survived better, and were heavier than offspring of control parents. One possible explanation for the more dominant behavior of these birds might be increased androgen/estrogen effects from the yolk during their embryonic phase leading to increased anabolism and androgenic behavior. Using cDNA microarrays, we found that some of the differential brain gene expression caused by stress tended to be mirrored in the offspring, indicating transgenerational effects. In particular, several immunoglobulin genes seemed to be affected similarly in both stressed parents and their offspring. Estradiol, but not corticoserone, testosterone, androstendion, or dihydrotestosterone, was significantly higher in egg yolk from stressed birds, suggesting a possible mechanism for these effects. Our findings suggest that stress may cause adaptive responses in feeding behavior, which may be transmitted to the offspring by means of epigenetic regulation of immune genes. This may in turn prepare the offspring for coping with an unpredictable environment.
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| 8. |
- Ramesh, Rashmi, 1984-, et al.
(författare)
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Dietary Sugar Shifts Mitochondrial Metabolism and Small RNA Biogenesis in Sperm
- 2023
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Ingår i: Antioxidants and Redox Signaling. - : MARY ANN LIEBERT, INC. - 1523-0864 .- 1557-7716. ; 38:16-18, s. 1167-1183
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Increasing concentrations of dietary sugar results in a linear accumulation of triglycerides in male Drosophila, while inducing a U-shaped obesity response in their offspring. Here, using a combination of proteomics and small RNA (sRNA) sequencing, we aimed at understanding the molecular underpinning in sperm for such plasticity.Results: Proteomic analysis of seminal vesicles revealed that increasing concentrations of dietary sugar resulted in a bell-shaped induction of proteins involved in metabolic/redox regulation. Using stains and in vivo redox reporter flies, this pattern could be explained by changes in sperm production of reactive oxygen species (ROS), more exactly mitochondria-derived H2O2. By quenching ROS with the antioxidant N-acetyl cysteine and performing sRNA-seq on sperm, we found that sperm miRNA is increased in response to ROS. Moreover, we found sperm mitosRNA to be increased in high-sugar diet conditions (independent of ROS). Reanalyzing our previously published data revealed a similar global upregulation of human sperm mitosRNA in response to a high-sugar diet, suggesting evolutionary conserved mechanisms.Innovation: This work highlights a fast response to dietary sugar in mitochondria-produced H2O2 in Drosophila sperm and identifies redox-sensitive miRNA downstream of this event.Conclusions: Our data support a model where changes in the sperm mitochondria in response to dietary sugar are the primary event, and changes in redox homoeostasis are secondary to mitochondrial ROS production. These data provide multiple candidates for paternal intergenerational metabolic responses as well as potential biomarkers for human male fertility.
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| 9. |
- Serpeloni, Fernanda, et al.
(författare)
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Experiencing community and domestic violence is associated with epigenetic changes in DNA methylation of BDNF and CLPX in adolescents
- 2020
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Ingår i: Psychophysiology. - : Blackwell. - 0048-5772 .- 1469-8986. ; 57:1
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Tidskriftsartikel (refereegranskat)abstract
- Experiencing violence changes behavior, shapes personalities, and poses a risk factor for mental disorders. This association might be mediated through epigenetic modifications that affect gene expression, such as DNA methylation. The present study investigated the impact of community and domestic violence on DNA methylation measured in saliva collected from 375 individuals including three generations: grandmothers (n = 126), mothers (n = 125), and adolescents (n = 124, 53% female). Using the Infinium HumanMethylation450 BeadChip array, in adolescents, we detected two CpG sites that showed an association of DNA methylation and lifetime exposure to community and domestic violence even after FDR correction: BDNF_cg06260077 (logFC -0.454, p = 3.71E-07), and CLPX_cg01908660 (logFC = -0.372, p = 1.38E-07). Differential DNA methylation of the CpG BDNF_cg06260077 associated with exposure to violence was also observed in the maternal but not the grandmaternal generation. BDNF (brain-derived neurotrophic factor) and CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit) genes are involved in neural development. Our results thus reveal altered molecular mechanisms of developmental and intergenerational trajectories in survivors of repeated violent experiences.
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| 10. |
- Örkenby, Lovisa, 1992-
(författare)
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Small non-coding RNA in early fly development : plasticity, interactions and improved bioinformatic tools
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- At fertilization, the male and female pronuclei undergo a transformation from germline to pluripotency as they fuse, marking the beginning of Drosophila embryogenesis. As the parental contributions decrease, the zygote takes control of its genome in a process called the maternal-to-zygotic transition (MZT). Several small non-coding RNAs (sncRNAs), a very large and diverse group of RNAs, have regulatory roles during this transition. This includes for example microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs). Regulation by miRNAs mainly occurs through mediating maternal mRNA degradation, while piRNAs operate by repressing transposable elements (TEs) and regulating the nanos-induced embryonic body axis determination.In this thesis, the complex and dynamic field of early Drosophila embryogenesis and sncRNAs are put in relation to the included papers. In Paper I, I explored the most stress-sensitive embryonic period and found that stress before the midblastula transition retains maternal miRNAs. These miRNAs impact zygotic gene activation by modulating the boundary factor Elba1, leading to compromised transcription control. Paper III examines the piRNA population during MZT. I find differences of unique piRNA sequences in embryos of different ages but not in target preferences, potentially highlighting the importance of constant repression of certain TEs. Paper II addresses specific difficulties with sncRNA seq data analysis and presents a bioinformatic framework to improve these analyses using a sequence-based strategy.This thesis highlights the intricate interplay of sncRNAs in the critical period of early Drosophila embryogenesis and offers insights into their regulatory roles.
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