To Örebro University

oru.seÖrebro universitets publikasjoner
Endre søk
Link to record
Permanent link

Direct link
Alternativa namn
Publikasjoner (10 av 40) Visa alla publikasjoner
Alijagic, A., Kotlyar, O., Larsson, M., Salihovic, S., Hedbrant, A., Eriksson, U., . . . Särndahl, E. (2024). Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals. Environment International, 183, Article ID 108412.
Åpne denne publikasjonen i ny fane eller vindu >>Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals
Vise andre…
2024 (engelsk)Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 183, artikkel-id 108412Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.

sted, utgiver, år, opplag, sider
Elsevier, 2024
Emneord
Additive manufacturing, GC-HRMS, High-throughput morphological profiling, Metabolomics, Nylon, Plastic additives
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-110605 (URN)10.1016/j.envint.2023.108412 (DOI)001153657900001 ()38183898 (PubMedID)2-s2.0-85183378556 (Scopus ID)
Forskningsfinansiär
Knowledge Foundation, 20160019; 20190107; 20220122; 20200017Swedish Research Council, 2022-06725; 2018-05973
Tilgjengelig fra: 2024-01-09 Laget: 2024-01-09 Sist oppdatert: 2024-03-05bibliografisk kontrollert
Ninyio, N., Schmitt, K., Sergon, G., Nilsson, C., Andersson, S. & Scherbak, N. (2024). Stable expression of HIV-1 MPER extended epitope on the surface of the recombinant probiotic bacteria Escherichia Coli Nissle 1917 using CRISPR/Cas9. Microbial Cell Factories, 23(1), Article ID 39.
Åpne denne publikasjonen i ny fane eller vindu >>Stable expression of HIV-1 MPER extended epitope on the surface of the recombinant probiotic bacteria Escherichia Coli Nissle 1917 using CRISPR/Cas9
Vise andre…
2024 (engelsk)Inngår i: Microbial Cell Factories, E-ISSN 1475-2859, Vol. 23, nr 1, artikkel-id 39Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Mucosal vaccines have the potential to induce protective immune responses at the sites of infection. Applying CRISPR/Cas9 editing, we aimed to develop a probiotic-based vaccine candidate expressing the HIV-1 envelope membrane-proximal external region (MPER) on the surface of E. coli Nissle 1917.

RESULTS: The HIV-1 MPER epitope was successfully introduced in the porin OmpF of the E. coli Nissle 1917 (EcN-MPER) and the modification was stable over 30 passages of the recombinant bacteria on the DNA and protein level. Furthermore, the introduced epitope was recognized by a human anti-HIV-1 gp41 (2F5) antibody using both live and heat-killed EcN-MPER, and this antigenicity was also retained over 30 passages. Whole-cell dot blot suggested a stronger binding of anti-HIV-1 gp41 (2F5) to heat-killed EcN-MPER than their live counterpart. An outer membrane vesicle (OMV) - rich extract from EcN-MPER culture supernatant was equally antigenic to anti-HIV-1 gp41 antibody which suggests that the MPER antigen could be harboured in EcN-MPER OMVs. Using quantitative ELISA, we determined the amount of MPER produced by the modified EcN to be 14.3 µg/108 cfu.

CONCLUSIONS: The CRISPR/Cas9 technology was an effective method for establishment of recombinant EcN-MPER bacteria that was stable over many passages. The developed EcN-MPER clone was devoid of extraneous plasmids and antibiotic resistance genes which eliminates the risk of plasmid transfer to animal hosts, should this clone be used as a vaccine. Also, the EcN-MPER clone was recognised by anti-HIV-1 gp41 (2F5) both as live and heat-killed bacteria making it suitable for pre-clinical evaluation. Expression of OmpF on bacterial surfaces and released OMVs identifies it as a compelling candidate for recombinant epitope modification, enabling surface epitope presentation on both bacteria and OMVs. By applying the methods described in this study, we present a potential platform for cost-effective and rational vaccine antigen expression and administration, offering promising prospects for further research in the field of vaccine development.

sted, utgiver, år, opplag, sider
BioMed Central (BMC), 2024
Emneord
CRISPR/Cas9, HIV-1, Membrane-proximal external region (MPER), Outer membrane protein F (OmpF), Probiotic
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-111380 (URN)10.1186/s12934-023-02290-0 (DOI)001157372700001 ()38311724 (PubMedID)2-s2.0-85184084053 (Scopus ID)
Forskningsfinansiär
Knowledge Foundation, 20200063Örebro University
Merknad

Correction: Stable expression of HIV-1 MPER extended epitope on the surface of the recombinant probiotic bacteria Escherichia Coli Nissle 1917 using CRISPR/Cas9. Ninyio, N., Schmitt, K., Sergon, G. et al. Microb Cell Fact 23, 75 (2024). https://doi.org/10.1186/s12934-024-02347-8

Tilgjengelig fra: 2024-02-05 Laget: 2024-02-05 Sist oppdatert: 2024-03-08bibliografisk kontrollert
Alijagic, A., Scherbak, N., Kotlyar, O., Karlsson, P., Wang, X., Odnevall, I., . . . Engwall, M. (2023). A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles. Cells, 12(2), Article ID 281.
Åpne denne publikasjonen i ny fane eller vindu >>A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
Vise andre…
2023 (engelsk)Inngår i: Cells, E-ISSN 2073-4409, Vol. 12, nr 2, artikkel-id 281Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

sted, utgiver, år, opplag, sider
MDPI, 2023
Emneord
Additive manufacturing, high-content screening (HCS), inflammation, multivariate analysis, nanoparticle emissions, new approach methodologies (NAMs), targeted metabolomics
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-103319 (URN)10.3390/cells12020281 (DOI)000916977400001 ()36672217 (PubMedID)2-s2.0-85146736511 (Scopus ID)
Merknad

Funding agency:

General Electric 20190107 20160019

Tilgjengelig fra: 2023-01-23 Laget: 2023-01-23 Sist oppdatert: 2024-03-05bibliografisk kontrollert
Scherbak, N. N., Kruse, R., Nyström, T. & Jendle, J. (2023). Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial. Diabetes & metabolism journal, 47(5), 668-681
Åpne denne publikasjonen i ny fane eller vindu >>Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial
2023 (engelsk)Inngår i: Diabetes & metabolism journal, ISSN 2233-6079, E-ISSN 2233-6087, Vol. 47, nr 5, s. 668-681Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Diabetes is a chronic disease with several long-term complications. Several glucose-lowering drugs are used to treat type 2 diabetes mellitus (T2DM), e.g., glimepiride and liraglutide, in which both having different modes of action. Circulating microRNAs (miRNAs) are suggested as potential biomarkers that are associated with the disease development and the effects of the treatment. In the current study we evaluated the effect of glimepiride, liraglutide on the expression of the circulating miRNAs.

METHODS: The present study is a post hoc trial from a previously randomized control trial comparing liraglutide versus glimepiride both in combination with metformin in subjects with T2DM, and subclinical heart failure. miRNAs were determined in the subjects' serum samples with next generation sequencing. Expression patterns of the circulating miRNAs were analyzed using bioinformatic univariate and multivariate analyses (clinical trial registration: NCT01425580).

RESULTS: Univariate analyses show that treatment with glimepiride altered expression of three miRNAs in patient serum, miR-206, miR-182-5p, and miR-766-3p. Both miR-182-5p and miR-766-3p were also picked up among the top contributing miRNAs with penalized regularised logistic regressions (Lasso). The highest-ranked miRNAs with respect to Lasso coefficients were miR-3960, miR-31-5p, miR-3613-3p, and miR-378a-3p. Liraglutide treatment did not significantly influence levels of circulating miRNAs.

CONCLUSION: Present study indicates that glucose-lowering drugs differently affect the expression of circulating miRNAs in serum in individuals with T2DM. More studies are required to investigate possible mechanisms by which glimepiride is affecting the expression of circulating miRNAs.

sted, utgiver, år, opplag, sider
Korean Diabetes Association, 2023
Emneord
Circulating microRNA, Diabetes mellitus, type 2, Glimepiride, Liraglutide
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-106587 (URN)10.4093/dmj.2022.0342 (DOI)001151423000006 ()37349083 (PubMedID)2-s2.0-85174408868 (Scopus ID)
Forskningsfinansiär
Novo Nordisk
Tilgjengelig fra: 2023-06-27 Laget: 2023-06-27 Sist oppdatert: 2024-02-14bibliografisk kontrollert
Scherbak, N., Kruse, R., Nyström, T. & Jendle, J. (2023). Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes Metab J 2023;47:668-81) [Letter to the editor]. Diabetes & metabolism journal, 47(6), 882-883
Åpne denne publikasjonen i ny fane eller vindu >>Glimepiride Compared to Liraglutide Increases Plasma Levels of miR-206, miR-182-5p, and miR-766-3p in Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes Metab J 2023;47:668-81)
2023 (engelsk)Inngår i: Diabetes & metabolism journal, ISSN 2233-6079, E-ISSN 2233-6087, Vol. 47, nr 6, s. 882-883Artikkel i tidsskrift, Letter (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
Korean Diabetes Association, 2023
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-110010 (URN)10.4093/dmj.2023.0355 (DOI)001175127000002 ()38043784 (PubMedID)2-s2.0-85178650647 (Scopus ID)
Tilgjengelig fra: 2023-12-04 Laget: 2023-12-04 Sist oppdatert: 2024-03-21bibliografisk kontrollert
Alijagic, A., Scherbak, N., Kotlyar, O., Karlsson, P., Persson, A., Hedbrant, A., . . . Engwall, M. (2022). Cell Painting unveils cell response signatures to (nano)particles formed in additive manufacturing. Paper presented at XVIth International Congress of Toxicology (ICT 2022) - UNITING IN TOXICOLOGY, Maastricht, The Netherlands, September 18-21, 2022. Toxicology Letters, 368(Suppl. 1), S226-S227, Article ID P17-01.
Åpne denne publikasjonen i ny fane eller vindu >>Cell Painting unveils cell response signatures to (nano)particles formed in additive manufacturing
Vise andre…
2022 (engelsk)Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, P17-01, Vol. 368, nr Suppl. 1, s. S226-S227, artikkel-id P17-01Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
sted, utgiver, år, opplag, sider
Elsevier, 2022
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-101516 (URN)10.1016/j.toxlet.2022.07.611 (DOI)000853725600549 ()
Konferanse
XVIth International Congress of Toxicology (ICT 2022) - UNITING IN TOXICOLOGY, Maastricht, The Netherlands, September 18-21, 2022
Tilgjengelig fra: 2022-09-29 Laget: 2022-09-29 Sist oppdatert: 2024-03-05bibliografisk kontrollert
Ninyio, N., Scherbak, N. & Andersson, S. (2022). Development and analysis of prospective anti-HIV probiotic vaccines. In: 19th Smögen Summer Symposium on Virology: Abstracts. Paper presented at 19th Smögen Summer Symposium on Virology, Smögen, August 25-27, 2022 (pp. 40-40). Virus- och Pandemifonden – Swedish Society for Virology
Åpne denne publikasjonen i ny fane eller vindu >>Development and analysis of prospective anti-HIV probiotic vaccines
2022 (engelsk)Inngår i: 19th Smögen Summer Symposium on Virology: Abstracts, Virus- och Pandemifonden – Swedish Society for Virology , 2022, s. 40-40Konferansepaper, Oral presentation with published abstract (Annet vitenskapelig)
Abstract [en]

Major improvements have been made in the treatment and prevention of HIV/AIDS. However, a prophylactic vaccine is still unavailable, and several vaccine-candidate trials yielded less than favourable results. Given that the HIV pandemic has not slowed down significantly, there is an urgent need for the development of an effective vaccine. The HIV-1 Gag protein, a key player in HIV particle assembly, is a suitable antigen for use in HIV vaccine development since antibodies targeting HIV-1 Gag will interfere with the replication of the virus. In our vaccine development strategy, it was important for us to develop a candidate for mucosal administration. This is because the mucosal route is the major site for HIV transmission and early viral replication, which is associated with extensive and rapid depletion of CD4+ T-cells in the Gut-Associated Lymphoid Tissue (GALT). Here, we transformed probiotic strains of Lactobacillus plantarum and Lactobacillus fermentum with the recombinant plasmid vectors pSIP409 and pSIP411 harbouring the HIV-1 GagM gene. Following electroporation, HIV-1 GagM expression was induced in the probiotics using peptide pheromone. Via PCR and sequencing, the presence of GagM was confirmed in the L. plantarum+ pSIP409-GagM and L. fermentum+ pSIP411-GagM clones. Protein expression was induced with peptide pheromone. Then, protein expression was confirmed by western blotting with goat anti-HIV p24 primary antibody and anti-goat secondary antibody. ELISA was also performed to confirm the antigenicity of the HIV-1 Gag antigen and to also quantify the antigen in the two Lactobacilli clones. Our results show that 1.5×109 CFU of L. plantarum+ pSIP409-GagM expressed 125μg of HIV-1 Gag and 1.9×109 CFU of L. fermentum+ pSIP411-GagM clones expressed 125μg of HIV-1 Gag respectively. In vitro digestion with pepsin, pancreatin and bile salts suggested that partial digestion of the probiotic vaccine candidates may occur when administered orally. Taken together, our probiotic HIV-1 vaccine candidates showed good prospects for further immunological analysis via animal trial.

sted, utgiver, år, opplag, sider
Virus- och Pandemifonden – Swedish Society for Virology, 2022
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-101079 (URN)
Konferanse
19th Smögen Summer Symposium on Virology, Smögen, August 25-27, 2022
Forskningsfinansiär
Knowledge Foundation
Tilgjengelig fra: 2022-09-05 Laget: 2022-09-05 Sist oppdatert: 2024-03-27bibliografisk kontrollert
Alijagic, A., Engwall, M., Särndahl, E., Karlsson, H., Hedbrant, A., Andersson, L., . . . Persson, A. (2022). Particle Safety Assessment in Additive Manufacturing: From Exposure Risks to Advanced Toxicology Testing. Frontiers in Toxicology, 4, Article ID 836447.
Åpne denne publikasjonen i ny fane eller vindu >>Particle Safety Assessment in Additive Manufacturing: From Exposure Risks to Advanced Toxicology Testing
Vise andre…
2022 (engelsk)Inngår i: Frontiers in Toxicology, E-ISSN 2673-3080, Vol. 4, artikkel-id 836447Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2022
Emneord
Adverse outcome, endocrine disruption, genotoxicity, industrial 3D printing, inflammation, mechanism of action, particle emissions
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-99004 (URN)10.3389/ftox.2022.836447 (DOI)001002826000001 ()35548681 (PubMedID)2-s2.0-85140953381 (Scopus ID)
Tilgjengelig fra: 2022-05-16 Laget: 2022-05-16 Sist oppdatert: 2024-03-05bibliografisk kontrollert
Scherbak, N., Ninyio, N., Nilsson, C., Rybicki, E. & Andersson, S. (2022). Production of anti-viral vaccines using probiotic bacteria. In: 19th Smögen Symposium on Virology: Abstracts: Viral Immunology and Vaccines II and III. Paper presented at 19th Smögen Symposium on Virology, Smögen, August 25-27, 2022 (pp. 16-16). Virus- och Pandemifonden – Swedish Society for Virology
Åpne denne publikasjonen i ny fane eller vindu >>Production of anti-viral vaccines using probiotic bacteria
Vise andre…
2022 (engelsk)Inngår i: 19th Smögen Symposium on Virology: Abstracts: Viral Immunology and Vaccines II and III, Virus- och Pandemifonden – Swedish Society for Virology , 2022, s. 16-16Konferansepaper, Oral presentation with published abstract (Fagfellevurdert)
Abstract [en]

The mucosal surfaces throughout the body are constantly exposed to microorganisms. The mucosal surfaces accommodate a large part of the body’s immune system. For effective vaccination, it is believed that direct immunization on mucosal surfaces will be more effective than the more conventional systemic immunization. Certain probiotic bacteria provide significant adjuvant effects that may be utilized for the desired immune response. Virus-like particles (VLPs) are complexes of viral proteins that without being infectious are efficient in mimicking the natural viral structures. While presenting the patterns of viral antigens, the VLPs have been shown to efficiently interact with dendritic cells and be effective in triggering the B and T-cell immunity. HIV-1 Gag is one of the most highly conserved structural antigens and contains several immunodominant T- and B-cell epitopes. Mosaic Gag protein matches 74% of 9-amino-acid potential epitopes in global Gag sequences thus maximizing the coverage of potential T-cell epitopes for a viral population.The current study aimed to develop probiotic strains of Lactobacillus plantarum NC8 and E. coli Nissle 1917 that produced recombinant mosaic HIV-1 Gag protein as VLPs.For the transient expression of the mosaic HIV-1 Gag protein (GagM), the gene-carrying expression vectors were transformed into the L. plantarum and in probiotic E.coli Nissle 1917. Protein expression of the GagM was shown to lead to the formation of the VLPs of the recombinant HIV-1 Gag proteins. This was confirmed through immunoblotting and transmission electron microscopy (TEM).Our study shows that probiotic lactobacteria can be developed to express HIV-1 Gag VLPs, which may be used for VLP production and potentially for vaccine delivery. Further evaluation of the concept is merited.

sted, utgiver, år, opplag, sider
Virus- och Pandemifonden – Swedish Society for Virology, 2022
HSV kategori
Forskningsprogram
Immunologi
Identifikatorer
urn:nbn:se:oru:diva-101080 (URN)
Konferanse
19th Smögen Symposium on Virology, Smögen, August 25-27, 2022
Prosjekter
Developvaccines@oru
Forskningsfinansiär
Knowledge Foundation
Tilgjengelig fra: 2022-09-05 Laget: 2022-09-05 Sist oppdatert: 2022-09-06bibliografisk kontrollert
Blanc, M., Antczak, P., Cousin, X., Grunau, C., Scherbak, N., Rüegg, J. & Keiter, S. (2021). The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio). Science of the Total Environment, 779, Article ID 146404.
Åpne denne publikasjonen i ny fane eller vindu >>The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio)
Vise andre…
2021 (engelsk)Inngår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 779, artikkel-id 146404Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The pyrethroid insecticide permethrin is widely used for agricultural and domestic purposes. Previous data indicated that it acts as a developmental neurotoxicant and can induce transgenerational effects in non-target organisms. However, associated underlying mechanisms remain unclear. The aim of this study was to investigate permethrin-related transgenerational effects in the zebrafish model, and to identify possible molecular mechanisms underlying inheritance. Zebrafish (F0) were exposed to permethrin during early-life (2 h post-fertilization up to 28 days). The F1 and F2 offspring generations were obtained by pairing exposed F0 males and females, and were bred unexposed. Locomotor and anxiety behavior were investigated, together with transcriptomic and epigenomic (DNA methylation) changes in brains. Permethrin exposed F0 fish were hypoactive at adulthood, while males from the F1 and F2 generations showed a specific decrease in anxiety-like behavior. In F0, transcriptomic data showed enrichment in pathways related to glutamatergic synapse activity, which may partly underlie the behavioral effects. In F1 and F2 males, dysregulation of similar pathways was observed, including a subset of differentially methylated regions that were inherited from the F0 to the F2 generation and indicated stable dysregulation of glutamatergic signaling. Altogether, the present results provide novel evidence on the transgenerational neurotoxic effects of permethrin, as well as mechanistic insight: a transient exposure induces persistent transcriptional and DNA methylation changes that may translate into transgenerational alteration of glutamatergic signaling and, thus, into behavioral alterations.

sted, utgiver, år, opplag, sider
Elsevier, 2021
Emneord
DNA methylation, Developmental neurotoxicity, Glutamatergic signaling, Pesticide, Transgenerational epigenetic inheritance
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-90673 (URN)10.1016/j.scitotenv.2021.146404 (DOI)000655687200016 ()33752003 (PubMedID)2-s2.0-85102882062 (Scopus ID)
Forskningsfinansiär
Knowledge FoundationHelge Ax:son Johnsons stiftelse
Merknad

Funding Agency:

French National Research Agency (ANR) ANR-10-LABX-04-01

Tilgjengelig fra: 2021-03-23 Laget: 2021-03-23 Sist oppdatert: 2021-06-18bibliografisk kontrollert
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-9713-2365