| 1. |
- Cao, Hao, 1988-, et al.
(författare)
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Developmental bisphenol A diglycidyl ether (BADGE) exposure causes cell over-proliferation in Drosophila
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Since the estrogenic activity of bisphenol A had been reported, the industry started to find a proper replacement. Bisphenol A diglycidyl ether (BADGE) is one of the derivatives of BPA which is used widely in epoxy resin manufactory. Recently, some studies have demonstrated the adverse effects of BADGE on reproduction and development. However, the knowledge of BADGE is still scarce. Because of its hydrolytic property, BADGE is usually detected at a low level in commodities and the influences seem to be underestimated. In our study, we use the whole transcriptome sequencing to assess the effects of developmental BADGE exposure on Drosophila melanogaster. Notably, the genes related to cell proliferation are significantly affected by BADGE exposure. More detailed, a group of mitotic genes, including string (stg, human CDC25A), Cyclin B (CycB, human CCNB1), Cyclin E (CycE, human CCNE1), and pan gu (png, human NEK11), are detectable overexpressed. Phenotypically, we observe that BADGE induces severe hemocytes over-proliferation in the 3rd instar larvae, but does not cause morphological damage of the larval lymph gland and blood circulation. In conclusion, we provide evidence to show the carcinogenic potential of BADGE and raise the concern of better understanding of xenobiotics.
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| 2. |
- Williams, Michael J., et al.
(författare)
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Exposure to the environmental pollutant bisphenol A diglycidyl ether (BADGE) causes cell over-proliferation in Drosophila
- 2020
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Ingår i: Environmental Science and Pollution Research. - : SPRINGER HEIDELBERG. - 0944-1344 .- 1614-7499. ; 27:20, s. 25261-25270
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A diglycidyl ether (BADGE), a derivative of bisphenol A (BPA), is widely used in the manufacture of epoxy resins as well as a coating on food containers. Recent studies have demonstrated the adverse effects of BADGE on reproduction and development in rodents and amphibians, but how BADGE affects biological activity is not understood. To gain a better understanding of the biological effects of BADGE exposure during development, we used the model organism Drosophila melanogaster and performed whole transcriptome sequencing. Interestingly, when Drosophila are raised on food containing BADGE, genes having significantly increased transcript numbers are enriched for those involved in regulating cell proliferation, including DNA replication and cell cycle control. Furthermore, raising larvae on BADGE-containing food induces hemocyte (blood cell) over-proliferation. This effect can be stimulated with even lower concentrations of BADGE if the hemocytes are already primed for cell proliferation by the expression of dominant active Ras GTPase. We conclude that chronic exposure to the xenobiotic BADGE throughout development can induce cell proliferation.
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| 3. |
- Konstantinidis, Evangelos, 1990-, et al.
(författare)
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Amyloid-beta accumulation in astrocytes affects their impact on neuronal function in a human iPSC-based model of Alzheimer’s disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Although Alzheimer’s disease (AD) is the leading cause of dementia worldwide, there are currently no treatments available that limit the neurodegeneration or slow down the disease progression. Hence, innovative therapeutic approaches are clearly required. The role of astrocytes in AD has recently received much attention, due to their central function in brain homeostasis and synaptic function. Accumulating evidence indicates that astrocytes may lose the ability to fulfil some of their physiological tasks when shifting towards an inflammatory state. Our previous data demonstrate that astrocytes can ingest large amounts of aggregated amyloid-beta (Aβ), but then store, rather than degrade, the ingested material. This incomplete degradation results in severe cellular stress, which could be of relevance for AD progression.Methods: In this study, we aimed to investigate how inclusions of aggregated Aβ in astrocytes affect their interplay with neurons, focusing on cellular viability and synaptic function. For this purpose, human induced pluripotent stem cell (hiPSC)-derived astrocytes were exposed to sonicated Αβ42 fibrils and their impact on hiPSC-derived neurons was analyzed by performing neuron-astrocyte co-cultures as well as additions of conditioned media or extracellular vesicles to pure neuronal cultures.Results: In the co-culture setup, the presence of Aβ inclusions led to an elevated clearance of dead cells by the astrocytes, indicating increased glial reactivity. In contrast, conditioned media from control, but not from Aβ-exposed astrocytes, benefited the wellbeing of neuronal monocultures. Furthermore, electrophysiological recordings showed a significant decrease in the frequency of excitatory post synaptic current (sEPSCs) in neurons co-cultured with Aβ-astrocytes compared to control astrocytes, while conditioned media from Aβ-exposed astrocytes had the opposite effect.Conclusions: Taken together, our results demonstrate that inclusions of aggregated Aβ affect the reactivity state of astrocytes, as well as their ability to support neuronal function.
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| 4. |
- Konstantinidis, Evangelos, 1990-, et al.
(författare)
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Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function
- 2023
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Ingår i: Journal of Neuroinflammation. - : Springer Nature. - 1742-2094. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAstrocytes are crucial for maintaining brain homeostasis and synaptic function, but are also tightly connected to the pathogenesis of Alzheimer’s disease (AD). Our previous data demonstrate that astrocytes ingest large amounts of aggregated amyloid-beta (Aβ), but then store, rather than degrade the ingested material, which leads to severe cellular stress. However, the involvement of pathological astrocytes in AD-related synaptic dysfunction remains to be elucidated.MethodsIn this study, we aimed to investigate how intracellular deposits of Aβ in astrocytes affect their interplay with neurons, focusing on neuronal function and viability. For this purpose, human induced pluripotent stem cell (hiPSC)-derived astrocytes were exposed to sonicated Αβ42 fibrils. The direct and indirect effects of the Αβ-exposed astrocytes on hiPSC-derived neurons were analyzed by performing astrocyte–neuron co-cultures as well as additions of conditioned media or extracellular vesicles to pure neuronal cultures.ResultsElectrophysiological recordings revealed significantly decreased frequency of excitatory post-synaptic currents in neurons co-cultured with Aβ-exposed astrocytes, while conditioned media from Aβ-exposed astrocytes had the opposite effect and resulted in hyperactivation of the synapses. Clearly, factors secreted from control, but not from Aβ-exposed astrocytes, benefited the wellbeing of neuronal cultures. Moreover, reactive astrocytes with Aβ deposits led to an elevated clearance of dead cells in the co-cultures.ConclusionsTaken together, our results demonstrate that inclusions of aggregated Aβ affect the reactive state of the astrocytes, as well as their ability to support neuronal function.
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