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| 2. |
- Jonasson, Erik, et al.
(författare)
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Tillväxt utan jobb?
- 2006
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Ingår i: Den problematiska tryggheten - välfärdsstaten under tre decennier. ; , s. 105-144
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Jönsson, Marie E, et al.
(författare)
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Activation of endogenous retroviruses during brain development causes an inflammatory response
- 2021
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Ingår i: EMBO Journal. - : EMBO Press. - 0261-4189 .- 1460-2075. ; 40:9
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV-derived proteins in aggregate-like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.
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| 4. |
- Norrman, Erik, et al.
(författare)
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Det svenska skattesystemet
- 1997
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Ingår i: Marknad och Politik. - 9171506829 ; , s. 283-331
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Bokkapitel (populärvet., debatt m.m.)
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| 5. |
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| 6. |
- Pålsson, Erik, 1975, et al.
(författare)
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Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls
- 2015
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X. ; 25:1, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Goran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. (C) 2014 Elsevier B.V. and ECNP. All rights reserved.
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| 7. |
- Södersten, Erik, et al.
(författare)
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A comprehensive map coupling histone modifications with gene regulation in adult dopaminergic and serotonergic neurons
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The brain is composed of hundreds of different neuronal subtypes, which largely retain their identity throughout the lifespan of the organism. The mechanisms governing this stability are not fully understood, partly due to the diversity and limited size of clinically relevant neuronal populations, which constitute a technical challenge for analysis. Here, using a strategy that allows for ChIP-seq combined with RNA-seq in small neuronal populations in vivo, we present a comparative analysis of permissive and repressive histone modifications in adult midbrain dopaminergic neurons, raphe nuclei serotonergic neurons, and embryonic neural progenitors. Furthermore, we utilize the map generated by our analysis to show that the transcriptional response of midbrain dopaminergic neurons following 6-OHDA or methamphetamine injection is characterized by increased expression of genes with promoters dually marked by H3K4me3/H3K27me3. Our study provides an in vivo genome-wide analysis of permissive/repressive histone modifications coupled to gene expression in these rare neuronal subtypes.
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| 8. |
- Södersten, Erik
(författare)
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On molecular mechanisms of neural differentiation and forebrain development
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Telencephalic development is an extraordinary complex process where neural structures of highly diverse cell compositions emerge as the result of multiple developmental strategies imposing tight regulation, balance and timing of gene expression. Embryonic telencephalic neural stem cells (NSCs) can form the major cell types found in the telencephalon, and are thus an excellent model for studying transcriptional control of lineage choice mechanisms in CNS development. In paper I, we show that a member of the BTB/POZ family, Zbtb20, is required for proper repression of genes involved in interneuron and oligodendrocyte differentiation as well as proliferation and cell cycle exit in NSCs. Zbtb20 was expressed in the subpallium in a Dlx and Mash1 overlapping fashion and interacted with the co-regulator SMRT. siRNA-mediated knockdown of Zbtb20 in NSCs modulated expression of key regulatory genes in control of differentiation and proliferation, including Dlx1/2/5 and p57kip2, thus affecting the outcome of cell fate acquisition in favor of oligodendrocytic differentiation. Zbtb20 protein was accumulated in regulatory regions of the Dlx1/2 bi-gene cluster along with a T3-dependent accumulation to the MBP M1 promoter. Furthermore, the zebrafish homolog to Zbtb20 appeared to be necessary for proper gastrulation and formation of neuroectoderm in vivo possibly due to precautious expression of p57kip2, analogous to the NSCs phenotype. In paper II, we suggest a novel role for the cyclin-dependent kinase inhibitor p57Kip2 as a context-dependent repressor of neurogenic transcription factors and telencephalic neuronal differentiation. p57Kip2 interacted with pro-neuronal basic helix-loop-helix factors such as Mash1. Increased levels of p57Kip2 inhibited Mash1 transcriptional activity in a cyclin-dependent kinase (CDK) independent manner and acted as a direct repressor in transcriptional assays. Proliferating telencephalic neural progenitors co-expressed basal levels of Mash1 and p57Kip2, and endogenous p57Kip2 accumulated transiently in the nuclei of NSCs during early stages of astrocyte differentiation, independent of cell-cycle exit and at times when Mash1 expression was still prominent. p57Kip2 repressed neuronal differentiation, but exerted little or no effect astroglial differentiation of NSCs. In paper III we propose that Zbtb45 is a novel regulator of glial differentiation. Zbtb45 mRNA was ubiquitously expressed in the developing CNS in mouse embryos but Zbtb45 mRNA knockdown in NSCs resulted in a rapid decrease in the expression of oligodendrocyte characteristic genes and significantly increased numbers of astrocytes. Zbtb45 mRNA knockdown in oligodendrocyte precursors completely inhibited oligodendrocyte differentiation upon mitogen withdrawal as assessed by a down-regulation of the expression of markers for oligodendrocytic differentiation such as CNPase, MBP and Sox10, whereas CD44 expression was found to be increased in all experiments. In paper IV we propose that the previously uncharacterized protein CXXC5 is acting as a BMP4 induced inhibitor of Wnt signaling in neural stem cells. CXXC5 expression overlapped with BMP4 adjacent to Wnt3a expression in the dorsal regions of the telencephalon. CXXC5 showed partial homology with Idax, shown to interact with the Wnt-signaling intermediate Dishevelled (Dvl). Indeed CXXC5 and Dvl colocalized in NSCs and interacted in vitro. CXXC5 over-expression attenuated Wnt signaling. Interestingly, BMP4-induced decrease in Axin2 levels was abolished by siRNA-mediated knockdown of CXXC5.
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| 9. |
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| 10. |
- Toskas, Konstantinos, et al.
(författare)
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PRC2-mediated repression is essential to maintain identity and function of differentiated dopaminergic and serotonergic neurons
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:34
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Tidskriftsartikel (refereegranskat)abstract
- How neurons can maintain cellular identity over an entire life span remains largely unknown. Here, we show that maintenance of identity in differentiated dopaminergic and serotonergic neurons is critically reliant on the Polycomb repressive complex 2 (PRC2). Deletion of the obligate PRC2 component, Eed, in these neurons resulted in global loss of H3K27me3, followed by a gradual activation of genes harboring both H3K27me3 and H3K9me3 modifications. Notably, H3K9me3 was lost at these PRC2 targets before gene activation. Neuronal survival was not compromised; instead, there was a reduction in subtype-specific gene expression and a progressive impairment of dopaminergic and serotonergic neuronal function, leading to behavioral deficits characteristic of Parkinson's disease and anxiety. Single-cell analysis revealed subtype-specific vulnerability to loss of PRC2 repression in dopamine neurons of the substantia nigra. Our study reveals that a PRC2-dependent nonpermissive chromatin state is essential to maintain the subtype identity and function of dopaminergic and serotonergic neurons.
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