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母体铅暴露会降低仔鼠大脑发育和认知相关蛋白的水平,同时伴随氧化应激、炎症反应和细胞凋亡的增加。

Maternal lead exposure decreases the levels of brain development and cognition-related proteins with concomitant upsurges of oxidative stress, inflammatory response and apoptosis in the offspring rats.

作者信息

Hossain Shahdat, Bhowmick Sujan, Jahan Sabrin, Rozario Liza, Sarkar Marzan, Islam Saiful, Basunia Mafroz Ahmed, Rahman Azizur, Choudhury Bazlul Karim, Shahjalal Hussain

机构信息

Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.

Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.

出版信息

Neurotoxicology. 2016 Sep;56:150-158. doi: 10.1016/j.neuro.2016.07.013. Epub 2016 Aug 1.

Abstract

The presence of lead (Pb) in fetal brain may affect brain development-related proteins. We studied whether gestational/lactational Pb-exposure affects oxidative stress, proinflammatory response, apoptosis and levels of brain development/cognition-related proteins, including presynaptic synaptosome-associated protein-25 (SNAP-25), postsynaptic density protein-95 (PSD-95), brain-derived neurotropic factor (BDNF), tyrosine receptor-kinase protein B (TrkB) and vesicular acetylcholine transporter (VAChT) in the offspring. Female Wistar rats were randomly divided into control and Pb-exposed mother groups. The Pb-exposed rats received 0.1% (w/v) Pb acetate via drinking water during pregnancy and lactation. Milk and mammary glands were collected from lactating mothers to measure milk/mammary gland levels of lipid peroxide (LPO), as indicator of oxidative stress and proinflammatory TNF-α. Afterwards, the pups were sacrificed to determine brain levels of Pb, LPO, TNF-α, cytochrome C, SNAP-25, PSD-95, BDNF, TrkB and VAChT. The levels of LPO and TNF-α increased in the milk/mammary glands of the Pb-exposed mothers, concurrently with increases in the levels of Pb, LPO, TNF-α and cytochrome C and decreases in the levels of SNAP-25, PSD-95, BDNF, TrkB and VAChT in the brains of their offspring. Our results demonstrate that Pb-exposure during development reduces the brain levels of PSD-95 and SNAP-25 (synaptogenesis-markers), with concomitant upsurges of oxidative stress, TNF-α and apoptosis in the offspring. Furthermore, BDNF-TrkB proteins that comprehend memory-related brain cognitions and/or VAChT that comprises cholinergic-neuromotor activities might be impaired by Pb-exposure. These findings provide evidence of toxic effects of Pb on brain development, at least, partially by decreasing the levels of PSD-95, SNAP-25 and other cognition-related proteins.

摘要

胎儿大脑中铅(Pb)的存在可能会影响与大脑发育相关的蛋白质。我们研究了孕期/哺乳期铅暴露是否会影响后代的氧化应激、促炎反应、细胞凋亡以及大脑发育/认知相关蛋白质的水平,这些蛋白质包括突触前突触小体相关蛋白25(SNAP - 25)、突触后致密蛋白95(PSD - 95)、脑源性神经营养因子(BDNF)、酪氨酸受体激酶蛋白B(TrkB)和囊泡乙酰胆碱转运体(VAChT)。将雌性Wistar大鼠随机分为对照组和铅暴露母鼠组。铅暴露组大鼠在怀孕和哺乳期通过饮用水摄入0.1%(w/v)的醋酸铅。从哺乳期母鼠收集乳汁和乳腺,以测量脂质过氧化物(LPO)的乳汁/乳腺水平,作为氧化应激和促炎肿瘤坏死因子-α(TNF-α)的指标。之后,处死幼崽以测定大脑中铅、LPO、TNF-α、细胞色素C、SNAP - 25、PSD - 95、BDNF、TrkB和VAChT的水平。铅暴露母鼠的乳汁/乳腺中LPO和TNF-α水平升高,同时其后代大脑中铅、LPO、TNF-α和细胞色素C水平升高,而SNAP - 25、PSD - 95、BDNF、TrkB和VAChT水平降低。我们的结果表明,发育期间的铅暴露会降低后代大脑中PSD - 95和SNAP - 25(突触形成标志物)的水平,同时伴随氧化应激、TNF-α和细胞凋亡的增加。此外,包含与记忆相关的大脑认知的BDNF - TrkB蛋白和包含胆碱能神经运动活动的VAChT可能会因铅暴露而受损。这些发现提供了证据,证明铅对大脑发育具有毒性作用,至少部分是通过降低PSD - 95、SNAP - 25和其他认知相关蛋白质的水平来实现的。

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