1,2-Dichloroethane causes anxiety and cognitive dysfunction in mice by disturbing GABA metabolism and inhibiting the cAMP-PKA-CREB signaling pathway.
Ecotoxicol Environ Saf
; 279: 116464, 2024 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-38759534
ABSTRACT
1,2-Dichloroethane (1,2-DCE) is a powerfully toxic neurotoxin, which is a common environmental pollutant. Studies have indicated that 1,2-DCE long-term exposure can result in adverse effects. Nevertheless, the precise mechanism remains unknown. In this study, behavioral results revealed that 1,2-DCE long-term exposure could cause anxiety and learning and memory ability impairment in mice. The contents of γ-aminobutyric acid (GABA) and glutamine (Gln) in mice's prefrontal cortex decreased, whereas that of glutamate (Glu) increased. With the increase in dose, the activities of glutamate decarboxylase (GAD) decreased and those of GABA transaminase (GABA-T) increased. The protein and mRNA expressions of GABA transporter-3 (GAT-3), vesicular GABA transporter (VGAT), GABA A receptor α2 (GABAARα2), GABAARγ2, K-Cl cotransporter isoform 2 (KCC2), GABA B receptor 1 (GABABR1), GABABR2, protein kinase A (PKA), cAMP-response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), c-fos, c-Jun and the protein of glutamate dehydrogenase (GDH) and PKA-C were decreased, while the expression levels of GABA transporter-1 (GAT-1) and Na-K-2Cl cotransporter isoform 1 (NKCC1) were increased. However, there was no significant change in the protein content of succinic semialdehyde dehydrogenase (SSADH). The expressions of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) contents were also reduced. In conclusion, the results of this study show that exposure to 1,2-DCE could lead to anxiety and cognitive impairment in mice, which may be related to the disturbance of GABA metabolism and its receptors along with the cAMP-PKA-CREB pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Transdução de Sinais
/
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
/
Proteínas Quinases Dependentes de AMP Cíclico
/
Dicloretos de Etileno
/
Ácido gama-Aminobutírico
Limite:
Animals
Idioma:
En
Revista:
Ecotoxicol Environ Saf
Ano de publicação:
2024
Tipo de documento:
Article