RT Journal Article
T1 Dopaminergic and serotoninergic systems as preferential targets of the pyrethroid tefluthrin exposure in the rat brain
A1 Maximiliano Guerra, Jorge Enrique
A1 Ares Lombán, Irma
A1 Martínez Caballero, Marta
A1 López Torres, Bernardo
A1 Martínez Larrañaga, María Rosa
A1 Anadón Navarro, Arturo Ramón
A1 Martínez Caballero, María Aranzazu
AB The monoaminergic systems dopamine (DA) and serotonin (5-HT) play important roles in neuromodulation, such as motor control, cognitive, affective, and neuroendocrine functions. In the present research study, we addressed the hypothesis that exposure to Type I pyrethroid tefluthrin may specifically target the dopaminergic and serotoninergic systems. Tefluthrin could modify brain monoamine neurotransmitters, DA and 5-HT levels as well as dopaminergic and serotoninergic signaling pathways. Adult male Wistar rats were treated with tefluthrin [2.2, 4.4 and 5.5 mg/kg bw, equivalent to 1/10, 1/5 and 1/4 of the acute oral rat lethal dose 50 (LD50) value] by oral gavage, six days. After last dose of tefluthrin, DA and 5-HT and metabolites levels were determined in brain regions (striatum, hippocampus, prefrontal cortex and hypothalamus). Tefluthrin induced a decrease of DA, 5-HT and metabolites contents, in a brain regional- and dose-related manner. The major decreases in DA and 5-HT contents were observed in prefrontal cortex tissue. Here, we studied that in vivo exposure to tefluthrin may alter DA and 5-HT neurotransmission in prefrontal cortex. Transcripts related to (i) dopaminergic [dopamine transporter 1 (Dat1), tyrosine hydroxylase (TH), dopamine receptors (Drd1, Drd2)], (ii) serotoninergic [serotonin transporter (SERT), tryptophan hydroxylase 2 (TPH2), serotonin receptors (5-HT1A, 5-HT2A)] and (iii) DA and 5-HT degradation [monoamine oxidases (MAOA, MAOB)] signaling pathways were investigated. Results showed that tefluthrin induced down-regulation of transcripts responsible for the synthesis and action of DA (TH, Drd1, Drd2) and 5-HT (SERT, TPH2). In contrast, tefluthrin treatment induced up-regulation of genes involved in DA transporter (Dat1), 5-HT receptors (5-HT1A, 5-HT2A) and monoamine oxidases (MAOA, MAOB). Given the integral roles of mitochondrial dysfunction and dopaminergic and serotoninergic alterations as hallmarks of neurodegenerative diseases, our data suggest that tefluthrin may be a candidate for pesticides contributing to neurodegenerative disorders pathogenesis by causing damage to the DA and 5-HT systems.
PB Elsevier
SN 0013-9351
YR 2024
FD 2024-01-17
LK https://hdl.handle.net/20.500.14352/102752
UL https://hdl.handle.net/20.500.14352/102752
LA eng
NO Maximiliano, J. E., Ares, I., Martínez, M., Lopez-Torres, B., Martínez-Larrañaga, M. R., Anadón, A., & Martínez, M. A. (2024). Dopaminergic and serotoninergic systems as preferential targets of the pyrethroid tefluthrin exposure in the rat brain. Environmental Research, 247, 118239.
NO Authorship contribution statement: Jorge-Enrique Maximiliano: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Irma Ares: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Marta Martínez: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Bernardo Lopez-Torres: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. María-Rosa Martínez-Larranaga: ˜ Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Arturo Anadon: ´ Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. María-Aranzazu ´ Martínez: Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.
DS Docta Complutense
RD 6 oct 2024