Publications
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Labba, Nils-Anders Johannes; Wæhler, Hallvard Austin; Houdaifi, Nora; Zosen, Denis; Haugen, Fred & Paulsen, Ragnhild Elisabeth Heimtun
[Show all 8 contributors for this article]
(2022).
Paracetamol perturbs neuronal arborization and disrupts the cytoskeletal proteins SPTBN1 and TUBB3 in both human and chicken in vitro models.
Toxicology and Applied Pharmacology.
ISSN 0041-008X.
449.
doi:
10.1016/j.taap.2022.116130.
Full text in Research Archive
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Epidemiological studies have linked long-term/high-dose usage of paracetamol (N-acetyl-para-aminophenol, APAP) during pregnancy to adverse neuropsychiatric outcomes, primarily attention-deficit hyperactive disorder (ADHD), in the offspring. Though variable, ADHD has been associated with phenotypic alterations characterized by reductions in grey matter densities and aberrations in structural connectivity, effects which are thought to originate in neurodevelopment. We used embryonic chicken cerebellar granule neurons (CGNs) and neuronally differentiating human NTERA2 cells (NT2Ns) to investigate the in vitro effects of APAP on cell viability, migration, neuritogenesis, and the intracellular levels of various proteins involved in neurodevelopment as well as in the maintenance of the structure and function of neurites. Exposure to APAP ranging from 100 to 1600 μM yielded concentration- and time-dependent reductions in cell viability and levels of neurite arborization, as well as reductions in the levels of the cytoskeletal protein β2-spectrin, with the highest APAP concentration resulting in between 50 and 75% reductions in the aforementioned metrics over the course of 72 h. Exposure to APAP also reduced migration in the NT2Ns but not CGNs. Moreover, we found concentration- and time-dependent increases in punctate aggregation of the cytoskeletal protein β3-tubulin following exposure to APAP in both cell model systems, with the highest APAP concentration approximately doubling the number of aggregates over 72–120 h. Our findings demonstrate that APAP negatively perturbs neurite arborization degree, with concurrent reductions in the protein levels of β2-spectrin and disruption of the integrity of β3-tubulin, both proteins of which play important roles in neuronal structure and function.
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Yadav, Ajay; Amber, Mazia; Zosen, Denis; Labba, Nils Anders; Huiberts, Eva Henriette Willemijn & Samulin-Erdem, Johanna Maria
[Show all 13 contributors for this article]
(2020).
A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) enhance nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells.
Toxicology Letters.
ISSN 0378-4274.
338,
p. 85–96.
doi:
10.1016/j.toxlet.2020.12.007.
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Disruption of neurite outgrowth is a marker for neurotoxicity. Persistent organic pollutants (POPs) are potential developmental neurotoxicants. We investigated their effect on neurite outgrowth in PC12 rat pheochromocytoma cells, in absence or presence of nerve growth factor (NGF), an inducer of neuronal differentiation. Cells were exposed for 72 h to a defined mixture of POPs with chemical composition and concentrations based on blood levels in the Scandinavian population. We also evaluated perfluorooctane sulfonic acid (PFOS) alone, the most abundant compound in the POP mixture. Only higher concentrations of POP mixture reduced tetrazolium salt (MTT) conversion. High-content analysis showed a decrease in cell number, but no changes for nuclear and mitochondrial cellular health parameters. Robust glutathione levels were observed in NGF-differentiated cells. Live imaging, using the IncuCyte ZOOM platform indicated ongoing cell proliferation over time, but slower in presence of NGF. The pollutants did not inhibit neuritogenesis, but rather increased NGF-induced neurite length. PFOS induced neurite outgrowth to about 50 % of the level seen with the POP mixture. Neither the POP mixture nor PFOS affected neurite length in the absence of NGF. Our observations indicate that realistic complex mixtures of environmental pollutants can affect neuronal connectivity via NGF-induced neurite outgrowth.
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Sørvik, Irene Beate; Solum, Eirik Johansson; Labba, Nils Anders; Hansen, Trond Vidar & Paulsen, Ragnhild Elisabeth
(2018).
Differential effects of some novel synthetic oestrogen analogs on oxidative PC12 cell death caused by serum deprivation.
Free radical research.
ISSN 1071-5762.
52(2),
p. 273–287.
doi:
10.1080/10715762.2018.1430363.
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Published
June 3, 2024 2:39 PM
- Last modified
June 3, 2024 2:39 PM