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

J 2024

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

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30108 Toxicology

Country of publisher

Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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

Citovat

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.

@article{2379118,
   author = {Kubíčková, Barbara and Martinková, Šárka and Bohačiaková, Dáša and Hilscherová, Klára},
   article_location = {CLARE},
   article_number = {January 2024},
   doi = {http://dx.doi.org/10.1016/j.toxlet.2023.12.004},
   keywords = {Developmental neurotoxicity; NSC; Retinoids; Differentiation; Anatoxin; Cyanotoxin},
   language = {eng},
   issn = {0378-4274},
   journal = {Toxicology Letters},
   title = {Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid},
   url = {https://www.sciencedirect.com/science/article/pii/S0378427423011116?via%3Dihub},
   volume = {391},
   year = {2024}
}

TY  - JOUR
ID  - 2379118
AU  - Kubíčková, Barbara - Martinková, Šárka - Bohačiaková, Dáša - Hilscherová, Klára
PY  - 2024
TI  - Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid
JF  - Toxicology Letters
VL  - 391
IS  - January 2024
SP  - 39-44
EP  - 39-44
PB  - Elsevier
SN  - 03784274
KW  - Developmental neurotoxicity
KW  - NSC
KW  - Retinoids
KW  - Differentiation
KW  - Anatoxin
KW  - Cyanotoxin
UR  - https://www.sciencedirect.com/science/article/pii/S0378427423011116?via%3Dihub
N2  - 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.
ER  -

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. \textit{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.

Detailed Information on Publication Record