Anxiety and Gene Expression Enhancement in Mice Exposed to Glyphosate-Based Herbicide

Toxics

Yassine Ait bali¹  Mohamed Bennis²  Saadia Ba-M’hamed²  Nour-eddine Kaikai²  Marco Sassoè-Pognetto³  Maurizio Giustetto³ 

[1] Department of Biology, Higher Normal School, University Mohamed V, Rabat 5118, Morocco;Laboratory of Pharmacology, Neurobiology, Anthropology, and Environment, Faculty of Sciences, Cadi Ayyad University, Marrakech 40000, Morocco;“Rita Levi-Montalcini” Department of Neuroscience, University of Turin, 10124 Turin, Italy;

关键词: glyphosate;    anxiety;    neuronal activation;    c-Fos;    pCREB;   

DOI  :  10.3390/toxics10050226

来源: DOAJ

【 摘 要 】

Growing evidence demonstrates that serotonin (5-HT) depletion increases activity in the amygdala and medial prefrontal cortex (mPFC), ultimately leading to anxiety behavior. Previously, we showed that glyphosate-based herbicides (GBHs) increased anxiety levels and reduced the number of serotoninergic fibers within the mPFCs and amygdalas of exposed mice. However, the impact of this 5-HT depletion following GBH exposure on neuronal activity in these structures is still unknown. In this study, we investigated the effects of GBH on immediate early gene (IEG) activation within the mPFCs and amygdalas of treated mice from juvenile age to adulthood and its subsequent effects on anxiety levels. Mice were treated for subchronic (6 weeks) and chronic (12 weeks) periods with 250 or 500 mg/kg/day of GBH and subjected to behavioral testing using the open field and elevated plus maze paradigms. Then, we analyzed the expression levels of c-Fos and pCREB and established the molecular proxies of neuronal activation within the mPFC and the amygdala. Our data revealed that repeated exposure to GBH triggers anxiogenic behavior in exposed mice. Confocal microscopy investigations into the prelimbic/infralimbic regions of the mPFC and in basolateral/central nuclei of the amygdala disclosed that the behavioral alterations are paralleled by a robust increase in the density and labelling intensity of c-Fos- and pCREB-positive cells. Taken together, these data show that mice exposed to GBH display the hyperactivation of the mPFC–amygdala areas, suggesting that this is a potential mechanism underlying the anxiety-like phenotype.

【 授权许可】

Unknown