Haj-Khlifa Asmaa, Oukhrib Mjid, Aziz Faissal, Boukhzar Loubna, Kissani Najib, Gamrani Halima, Bouyatas Moulay Mustapha
Neuroscience, Pharmacology and Environment Unit (NPEU), Faculty of Sciences Semlalia. Laboratory of Experimental, Clinical and Environmental Neurosciences, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco.
Laboratory of Water, Biodiversity, and Climate Change, Faculty of Sciences Semlalia, Cadi Ayyad University, BP 2390, 40000, Marrakech, Morocco.
Biol Trace Elem Res. 2025 Jun 4. doi: 10.1007/s12011-025-04683-1.
Lead (Pb) is an environmental metal with toxic effects primarily targeting the central nervous system (CNS). Early-life exposure is linked to long-term behavioral and cognitive impairments. This study aims to evaluate the behavioral effects of Pb exposure during gestation and lactation and investigate the neuroprotective effect of the aqueous extract of Ononis natrix (AEON), a medicinal plant recognized for its antioxidant and anti-inflammatory properties, selected for its potential to counteract Pb-induced neurological damage. Pregnant mice were assigned to four groups: control, Pb-exposed (1 g/L in drinking water), and two groups receiving AEON (100 mg/kg and 500 mg/kg) by oral gavage alongside Pb from the first day of gestation until the end of lactation. Reproductive parameters were measured, such as fertility rate, gestation period, and offspring viability. Sensorimotor development was assessed using negative geotaxis, surface righting reflex, cliff avoidance, and suspension test. In adulthood, neurobehavioral functions such as anxiety-related behavior, locomotion, memory, depression-like behavior, and motor performance were assessed. We also measured markers of oxidative stress, notably catalase (CAT) and malondialdehyde (MDA), in the whole brain, hippocampus, and prefrontal cortex. Our results showed that Pb exposure led to a significant reduction in gestation period in pregnant females and considerably disrupted sensorimotor development in the offspring. In adulthood, Pb-exposed mice exhibited pronounced anxiety-like behavior and depressive-like symptoms, along with hyperactivity and impaired motor coordination. These dysfunctions were correlated with increased CAT activity and MDA levels in different brain regions. However, co-administration of AEON improved reproductive parameters, enhanced sensorimotor functions, normalized neurobehavioral performance in adulthood, and restored disrupted oxidative stress markers. These findings provide the first evidence of AEON's efficacy in mitigating developmental Pb-induced neurotoxicity, highlighting its potential as a novel neuroprotective agent and paving the way for future therapeutic strategies.
铅（Pb）是一种环境金属，其毒性作用主要针对中枢神经系统（CNS）。生命早期接触铅与长期行为和认知障碍有关。本研究旨在评估孕期和哺乳期接触铅对行为的影响，并研究药用植物海滨棘豆水提取物（AEON）的神经保护作用。海滨棘豆因其抗氧化和抗炎特性而闻名，因其具有对抗铅诱导的神经损伤的潜力而被选用。将怀孕小鼠分为四组：对照组、铅暴露组（饮用水中含1 g/L铅），以及从妊娠第一天到哺乳期结束通过口服灌胃同时给予铅的两组AEON组（100 mg/kg和500 mg/kg）。测量生殖参数，如生育率、妊娠期和后代活力。使用负趋地性、表面翻正反射、悬崖回避和悬吊试验评估感觉运动发育。在成年期，评估神经行为功能，如焦虑相关行为、运动、记忆、抑郁样行为和运动表现。我们还测量了全脑、海马体和前额叶皮质中氧化应激的标志物，特别是过氧化氢酶（CAT）和丙二醛（MDA）。我们的结果表明，铅暴露导致怀孕雌性小鼠的妊娠期显著缩短，并严重扰乱了后代的感觉运动发育。在成年期，铅暴露小鼠表现出明显的焦虑样行为和抑郁样症状，以及多动和运动协调受损。这些功能障碍与不同脑区中CAT活性增加和MDA水平升高相关。然而，联合给予AEON改善了生殖参数，增强了感觉运动功能，使成年期神经行为表现正常化，并恢复了紊乱的氧化应激标志物。这些发现首次证明了AEON在减轻发育性铅诱导的神经毒性方面的功效，突出了其作为新型神经保护剂的潜力，并为未来的治疗策略铺平了道路。
