Manganese-induced miR-125b-2-3p promotes anxiety-like behavior via TFR1-mediated ferroptosis.
Environ Pollut
; 344: 123255, 2024 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-38159631
ABSTRACT
The toxic effects of excessive manganese (Mn) levels in the environment have led to a severe public health concern. Ferroptosis is a newly form of cell death relying on iron, inherent to pathophysiological processes of psychiatric disorders, such as anxiety and depression-like behaviors. Excessive Mn exposure causes various neurological effects, including neuronal death and mood disorders. Whether Mn exposure causes anxiety and depression-like behaviors, and the underlying mechanisms of Mn-induced ferroptosis have yet to be determined. Here, Mn-exposed mice showed anxiety-like behavior. We also confirmed the accumulation of ferrous ion (Fe2+), lipid peroxidation, and depletion of antioxidant defense system both in vitro and in vivo Mn-exposed models, suggesting that Mn exposure can induce ferroptosis. Furthermore, Mn exposure downregulated the expression of miR-125b-2-3p. In turn, overexpression of miR-125b-2-3p alleviated the Mn-induced ferroptosis by targeting Transferrin receptor protein 1 (TFR1). In summary, this novel study established the propensity of Mn to cause anxiety-like behavior, an effect that was regulated by miR-125b-2-3p and ensuing ferroptosis secondary to the targeting of TFR1. These results offer promising targets for the prevention and treatment of Mn-induced neurotoxicity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Ferroptosis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Environ Pollut
Asunto de la revista:
SAUDE AMBIENTAL
Año:
2024
Tipo del documento:
Article
País de afiliación:
China