Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid

KUBÍČKOVÁ, Barbara, Šárka MARTINKOVÁ, Dáša BOHAČIAKOVÁ and Klára HILSCHEROVÁ. Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid. Toxicology Letters. CLARE: Elsevier, 2024, vol. 391, January 2024, p. 39-44. ISSN 0378-4274. Available from: https://dx.doi.org/10.1016/j.toxlet.2023.12.004.

Basic information

• Original name: Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid
• Authors: KUBÍČKOVÁ, Barbara (203 Czech Republic, belonging to the institution), Šárka MARTINKOVÁ (203 Czech Republic, belonging to the institution), Dáša BOHAČIAKOVÁ (703 Slovakia, belonging to the institution) and Klára HILSCHEROVÁ (203 Czech Republic, guarantor, belonging to the institution).
• Edition: Toxicology Letters, CLARE, Elsevier, 2024, 0378-4274.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30108 Toxicology
• Country of publisher: Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 3.500 in 2022
• Organization unit: Faculty of Science
• Doi: http://dx.doi.org/10.1016/j.toxlet.2023.12.004
• UT WoS: 001138116200001
• Keywords in English: Developmental neurotoxicity; NSC; Retinoids; Differentiation; Anatoxin; Cyanotoxin
• Tags: 14110517
• Tags: International impact, Reviewed

Abstract

Cyanobacterial blooms are increasing in frequency and intensity globally, and impacting recreational waters as well as waters used for drinking water provisioning. They are sources of bioactive metabolites including retinoids and the neurotoxin anatoxin-a. Here, we investigated the effects of anatoxin-a on a differentiating in vitro human neural stem cell model previously characterised with retinoic acids. Effects on protein and gene expression upon exposure for 9 or 18 days to anatoxin-a alone or in co-exposure with all-trans retinoic acid were evaluated using a panel of neural and glial differentiation biomarkers. Anatoxin-a did not cause distinct developmental neuro-toxicity alone, or in co-exposure with retinoic acid. However, in line with its excitotoxicity, in co-exposure with 200 nM all-trans retinoic acid it reduced the differentiation of acetylcholinergic neuron subtypes in the culture at 1000 nM (highest tested concentration). While this could have substantial functional implications for the developing nervous system, there is no indication for developmental neurotoxicity beyond its (excito-)toxicity to acetylcholinergic neurons, which only occurred in co-exposure to all-trans retinoic acid.

Links

• EF17_043/0009632, research and development project: Name: CETOCOEN Excellence
• LM2023069, research and development project: Name: Výzkumná infrastruktura RECETOX

Investor: Ministry of Education, Youth and Sports of the CR, RECETOX research infrastructure

• LX22NPO5107, research and development project: Name: Národní ústav pro neurologický výzkum

Investor: Ministry of Education, Youth and Sports of the CR, 5.1 EXCELES

• 722493, interní kód MU: Name: Natural Toxins and Drinking Water Quality - From Source to Tap (Acronym: NaToxAq)

Investor: European Union, MSCA Marie Skłodowska-Curie Actions (Excellent Science)

• 857560, interní kód MU(CEP code: EF17_043/0009632): Name: CETOCOEN Excellence (Acronym: CETOCOEN Excellence)

Investor: European Union, Spreading excellence and widening participation