Yu Zhe, Iyer Laxmi, Swiercz Adam P, Paronett Elizabeth, Ramadan Manelle, Marvar Paul J, Posnack Nikki Gillum
Department of Pharmacology and Physiology, George Washington University, Washington, DC.
Department of Anatomy, Physiology and Genetics, Uniformed Services University Health Sciences, Bethesda, Maryland.
Biol Psychiatry Glob Open Sci. 2023 Jul 21;4(1):203-212. doi: 10.1016/j.bpsgos.2023.07.002. eCollection 2024 Jan.
There is a growing importance for environmental contributions to psychiatric disorders and understanding the impact of the exposome (i.e., pollutants and toxins). For example, increased biomonitoring and epidemiological studies suggest that daily phthalate chemical exposure contributes to neurological and behavioral abnormalities; however, these mechanisms remain poorly understood. Therefore, the current study was aimed at examining the effects of chronic phthalate exposure on rodent anxiety behaviors and cognition and the impact on hypothalamic-pituitary-adrenal axis function.
Adult male mice (C57BL6/J) were administered MEHP via drinking water (1 mg/mL), and anxiety-like behavior and cognition combined with hypothalamic-pituitary-adrenal axis and inflammatory assays were assessed after 3 weeks of MEHP exposure.
MEHP-treated mice exhibited enhanced generalized anxiety-like behaviors, as demonstrated by reduced time spent in the open-arm of the elevated plus maze and center exploration in the open field. Tests of spatial memory and cognition were unchanged. Following MEHP administration, circulating levels of corticosterone and proinflammatory cytokines were significantly increased, while at the tissue level, there were MEHP-dependent reductions in glucocorticoid metabolism genes and .
These data suggest that chronic MEHP exposure leads to enhanced generalized anxiety behaviors independent of rodent measures of cognition and memory, which may be driven by MEHP-dependent effects on hypothalamic-pituitary-adrenal axis and peripheral glucocorticoid metabolism function.
环境因素对精神疾病的影响以及对暴露组（即污染物和毒素）影响的理解正变得越来越重要。例如，生物监测和流行病学研究的增加表明，每日邻苯二甲酸酯化学物质暴露会导致神经和行为异常；然而，这些机制仍知之甚少。因此，本研究旨在探讨慢性邻苯二甲酸酯暴露对啮齿动物焦虑行为和认知的影响以及对下丘脑 - 垂体 - 肾上腺轴功能的影响。
成年雄性小鼠（C57BL6/J）通过饮用水给予单（2-乙基己基）邻苯二甲酸酯（MEHP，1 mg/mL），在MEHP暴露3周后评估焦虑样行为和认知，并结合下丘脑 - 垂体 - 肾上腺轴和炎症检测。
MEHP处理的小鼠表现出增强的广泛性焦虑样行为，高架十字迷宫开放臂停留时间减少和旷场试验中央探索减少证明了这一点。空间记忆和认知测试未发生变化。给予MEHP后，循环中的皮质酮和促炎细胞因子水平显著升高，而在组织水平上，糖皮质激素代谢基因有MEHP依赖性降低。
这些数据表明，慢性MEHP暴露导致增强的广泛性焦虑行为，独立于啮齿动物的认知和记忆指标，这可能由MEHP对下丘脑 - 垂体 - 肾上腺轴和外周糖皮质激素代谢功能的依赖性作用所驱动。
