Ait Bali Yassine, Kaikai Nour-Eddine, Ba-M'hamed Saadia, Sassoè-Pognetto Marco, Giustetto Maurizio, Bennis Mohamed
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.
Toxics. 2022 Apr 29;10(5):226. doi: 10.3390/toxics10050226.
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.
越来越多的证据表明，血清素（5-羟色胺，5-HT）耗竭会增加杏仁核和内侧前额叶皮质（mPFC）的活性，最终导致焦虑行为。此前，我们发现基于草甘膦的除草剂（GBHs）会增加暴露小鼠的焦虑水平，并减少其mPFC和杏仁核内血清素能纤维的数量。然而，GBH暴露后这种5-HT耗竭对这些结构中神经元活动的影响仍不清楚。在本研究中，我们调查了GBH对从幼年到成年的受试小鼠mPFC和杏仁核内即刻早期基因（IEG）激活的影响及其对焦虑水平的后续影响。用250或500毫克/千克/天的GBH对小鼠进行亚慢性（6周）和慢性（12周）处理，并使用旷场和高架十字迷宫范式进行行为测试。然后，我们分析了c-Fos和pCREB的表达水平，并建立了mPFC和杏仁核内神经元激活的分子指标。我们的数据显示，反复接触GBH会引发暴露小鼠的焦虑行为。对mPFC的前边缘/边缘下区域以及杏仁核的基底外侧/中央核进行的共聚焦显微镜研究发现，行为改变与c-Fos和pCREB阳性细胞的密度和标记强度的显著增加平行。综上所述，这些数据表明，暴露于GBH的小鼠表现出mPFC-杏仁核区域的过度激活，这表明这是焦虑样表型的潜在机制。
