Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 St., Szczecin, 70-111 Szczecin, Poland.
Department of Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 St., 70-111 Szczecin, Poland.
Int J Mol Sci. 2020 Feb 6;21(3):1083. doi: 10.3390/ijms21031083.
Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre- and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum.
Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1β, IL-6, transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB).
In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1β, IL-6, TGF-β, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression.
Chronic pre- and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups.
铅（Pb）是一种重金属，具有确凿的神经毒性。暴露对发育期前和新生儿期的大脑尤其危险。其神经毒性的一种假设机制是诱导炎症。本研究分析了发育期大鼠幼仔暴露于 Pb 对大脑前皮质、海马和小脑选定细胞因子和前列腺素浓度的影响。
从妊娠第一天到出生后第 21 天，自由饮用 0.1%醋酸铅（PbAc），导致大鼠幼仔血液中的 Pb 浓度达到疾病控制与预防中心（CDC）认为对人类安全的阈值以下（10µg/dL）。酶联免疫吸附测定（ELISA）法用于测定白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、转化生长因子-β（TGF-β）、前列腺素 E2（PGE2）和血栓素 B2（TXB2）的水平。Western blot 和实时定量 PCR 用于测定环氧化酶 COX-1 和 COX-2 的表达水平。最后，Western blot 用于测定核因子 kappa B（NF-κB）的水平。
在所有研究的大脑结构（大脑前皮质、海马和小脑）中，Pb 的给药导致所有研究的细胞因子和前列腺素（IL-1β、IL-6、TGF-β、PGE2 和 TXB2）显著增加。所有研究的大脑结构中 COX-1 和 COX-2 的蛋白和 mRNA 表达增加，NF-κB 表达也增加。
慢性发育期前和新生儿期暴露于 Pb 会在大鼠幼仔的大脑前皮质、海马和小脑引起神经炎症。
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