Miglioranza Elena, Rullo Laura, Alvente Sara, Bastianini Stefano, Coraci Dario, Lo Martire Viviana, Losapio Loredana Maria, Matteoli Gabriele, Morosini Camilla, Volino Emilia, Silvani Alessandro, Rimondini Roberto, Candeletti Sanzio, Romualdi Patrizia, Zoccoli Giovanna, Berteotti Chiara
PRISM Lab, Department of Biomedical and Neuromotor Sciences, and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, S. Orsola University Hospital, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
PLoS One. 2025 Aug 1;20(8):e0328581. doi: 10.1371/journal.pone.0328581. eCollection 2025.
Early-life exposure to environmental stressors may increase the risk of disease later in life. Chlorpyrifos (CPF), a widely used pesticide and acetylcholinesterase inhibitor, can cross the placental barrier and can be found in breast milk, leading to excessive cholinergic stimulation. Acetylcholine is involved in sleep and respiratory regulation. The main objective of this study was to investigate whether perinatal CPF exposure affects sleep-related breathing together with promotion of neuroinflammatory processes in adulthood. To explore these effects, CPF (5 mg/kg/day) or vehicle was administered orally to dams from mating to weaning. The offspring were not directly treated. At 17-18 weeks of age, male and female offspring underwent electroencephalographic and electromyographic electrode implantation to monitor sleep-wake cycles. Recordings were conducted over 48 hours in home cages, and for 7 hours in a plethysmographic chamber to assess sleep-related breathing pattern. At the end of recordings, hippocampal tissues were collected for gene expression analysis via real-time PCR. Results revealed that CPF perinatal exposure increased sighs and apneas during sleep in adult mice, especially in female. Additionally, expression of pro-inflammatory cytokines was upregulated while expression of peroxisome proliferator-activated receptor genes was downregulated in the hippocampus of female mice born to CPF-treated dams. These findings suggest that perinatal CPF exposure can induce long-lasting alterations in sleep-related respiratory patterns and hippocampal inflammatory responses, with a sex-specific susceptibility-females being more affected. This highlights the perinatal period as a critical window of vulnerability to environmental toxicants such as pesticides. The results support the hypothesis that adult sleep and brain inflammation phenotypes may be modulated by early-life chemical exposures during pregnancy and lactation.
生命早期暴露于环境应激源可能会增加日后患病的风险。毒死蜱（CPF）是一种广泛使用的杀虫剂和乙酰胆碱酯酶抑制剂，它可以穿过胎盘屏障，并存在于母乳中，导致胆碱能过度刺激。乙酰胆碱参与睡眠和呼吸调节。本研究的主要目的是调查围产期CPF暴露是否会影响与睡眠相关的呼吸，并促进成年期的神经炎症过程。为了探究这些影响，从交配到断奶期间，给母鼠口服CPF（5毫克/千克/天）或赋形剂。子代未直接接受处理。在17 - 18周龄时，对雄性和雌性子代进行脑电图和肌电图电极植入，以监测睡眠 - 觉醒周期。在家笼中进行48小时的记录，并在体积描记室中进行7小时的记录，以评估与睡眠相关的呼吸模式。记录结束时，收集海马组织通过实时PCR进行基因表达分析。结果显示，围产期暴露于CPF会增加成年小鼠睡眠期间的叹息和呼吸暂停，尤其是雌性小鼠。此外，在CPF处理的母鼠所生的雌性小鼠海马中，促炎细胞因子的表达上调，而过氧化物酶体增殖物激活受体基因的表达下调。这些发现表明，围产期CPF暴露可诱导与睡眠相关的呼吸模式和海马炎症反应的长期改变，具有性别特异性易感性——雌性受影响更大。这突出了围产期作为对农药等环境毒物易感性的关键窗口期。结果支持了这样的假设，即成年期的睡眠和脑炎症表型可能受到孕期和哺乳期早期化学物质暴露的调节。
