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大鼠发育期氟暴露影响记忆保留,导致类似抑郁的行为,并引起子代大鼠大脑的生化变化。

Rat developmental fluoride exposure affects retention memory, leads to a depressive-like behavior, and induces biochemical changes in offspring rat brains.

机构信息

Laboratorio de Toxicología, Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca CP8000, Argentina.

Laboratorio de Toxicología, Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca CP8000, Argentina.

出版信息

Neurotoxicology. 2022 Dec;93:222-232. doi: 10.1016/j.neuro.2022.10.006. Epub 2022 Oct 10.

Abstract

Water is the principal source of human exposure to fluoride (F). The high permeability of the placenta and blood-brain barrier to F during the intrauterine life up to the end of lactation may be crucial to neurological fetus development. Therefore, this study explores the effects of 5 and 10 mg/l F exposure during entire gestation and lactation periods, through neurobehavioral and biochemical tests performed on 90-day-old male offspring rats. The present study shows that pre and peri-natal exposure to F doses that are in the range of those found in groundwater sources in Argentina affects long-term memory and leads to a depressive-like behavior in 90-day-old male pup. Furthermore, the purpose of the investigation was to find out the possible biochemical changes through which the pre and peri-natal F-administration could generate such behavioral variations. We found alterations in transaminases, acetylcholinesterase, and alkaline phosphatase enzymes activity in specific brain areas (the prefrontal cortex, the striatum, and the hippocampus), together with findings regarding misbalanced oxidative stress. In conclusion, F exposure during the early stages of rat development alters brain-oxidative stress markers as well as the activity of enzymes implicated in cholinergic and glutamatergic systems. These molecular changes could contribute to the neurobehavioral alterations described in the present investigation.

摘要

水是人类接触氟化物 (F) 的主要来源。在宫内生命期直至哺乳期,胎盘和血脑屏障对 F 的高通透性可能对胎儿神经系统的发育至关重要。因此,本研究通过对 90 日龄雄性仔鼠进行神经行为学和生化测试,探讨了整个妊娠期和哺乳期内暴露于 5 和 10mg/l F 的影响。本研究表明,产前和围产期暴露于与阿根廷地下水中发现的氟化物剂量相当的剂量会影响长期记忆,并导致 90 日龄雄性幼鼠出现类似抑郁的行为。此外,研究的目的是找出可能的生化变化,通过这些变化,产前和围产期的 F 给药可能会产生这种行为变化。我们发现特定脑区(前额叶皮层、纹状体和海马体)中转氨酶、乙酰胆碱酯酶和碱性磷酸酶的活性发生改变,同时还发现氧化应激失衡。总之,在大鼠发育的早期阶段暴露于 F 会改变大脑氧化应激标志物以及参与胆碱能和谷氨酸能系统的酶的活性。这些分子变化可能有助于解释本研究中描述的神经行为改变。

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