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Lanthanum (La) can damage the blood brain barrier when it enters the brain tissue, causing learning and memory dysfunction. Currently, few studies have focused on La-induced oxidative stress in choroid plexus epithelial cells, which can severely impair the normal function of the blood-cerebrospinal fluid barrier (BCSFB) and ultimately cause central nervous system dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element(ARE) signaling pathway is one of the major antioxidant systems and is vital in protecting cells against oxidative injury in rodents. In this study, Z310 cells were employed to construct BCSFB in vitro and treated with lanthanum chloride (LaCl 3 ); meanwhile, 40 μmol/L tert-butylhydroquinone and the corresponding concentration of LaCl 3 was used as the intervention groups. The results showed that LaCl 3 treatment markedly decreased Z310 cell viability, increased the necrosis rate, and then reduced the transepithelial electrical resistance value of BCSFB in vitro; reactive oxygen species levels gradually increased, catalase and glutathione peroxidase activities decreased; furthermore, Nrf2 was significantly downregulated, and the expression of Nrf2 downstream genes such as heme oxygenase1, NADP(H): dehydrogenase quinone1, glutathione thiotransferase etc. noticeably decreased; in addition, interleukin-1β and tumour necrosis factor-α associated with Nrf2 activation noticeably increased. However, tert-butylhydroquinone could activate the Nrf2/AER signaling pathway and attenuate the Z310 cell oxidative damage induced by LaCl 3 . Thus, the Nrf2/ARE signaling pathway is probably involved in weakening the BCSFB in vitro that is created by La-induced oxidative stress. Tert-butylhydroquinone can activate this pathway to reverse severe oxidative damage, which significantly strengthen the function of BCSFB., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lanthanum can induce neurotoxicity and impair cognitive function; therefore, research on the mechanism by which the ability to learning and memory is decreased by lanthanum is vitally important for protecting health. Microglia are a type of neuroglia located throughout the brain and spinal cord that play an important role in the central nervous system. When overactive, these cells can cause the excessive production of inflammatory cytokines that can damage neighboring neurons. The purpose of this study was to explore the effect of lanthanum in the form of lanthanum chloride (LaCl 3 ) on learning and the memory of mice and determine whether there is a relationship between hippocampal neurons or learning and memory damage and excessive production of inflammatory cytokines. Four groups of pregnant Chinese Kun Ming mice were exposed to 0, 18, 36, or 72 mM LaCl 3 in their drinking water during lactation. The offspring were then exposed to LaCl 3 in the breast milk at birth until weaning and then exposed to these concentrations in their drinking water for 2 months after weaning. The results showed that LaCl 3 impaired learning and memory in mice and injured their neurons, activated the microglia, and significantly overregulated the mRNA and protein expression of tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, and nitric oxide in the hippocampus. The results of this study suggest that lanthanum can impair learning and memory in mice, possibly by over-activating the microglia., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Lanthanum is a rare earth element which can have adverse effects on the central nervous system (CNS). However, the mechanisms of these effects are not fully understood. The activated microglia plays an important role in the pathogenesis of neurodegenerative diseases and thus could be involved in mediating the toxic effects of lanthanum on the CNS. Nuclear factor-kappa B (NF-κB) is a critical nuclear factor which regulates the expression of inflammatory mediators in the activated microglia. This study investigated the effects of lanthanum chloride (LaCl3) on the NF-κB signaling pathway and explored the relationship between the microglia activation and neuron damage induced by La in vitro. The results showed that BV2 microglial cells treated with 0, 0.05, 0.1 or 0.2 mM LaCl3 could up-regulate the expression of Iba1 protein, a marker of microglia activation, and of p-IKKαβ and p-IκBα in a dose-dependent manner. La could also increase the translocation of the NF-κB p65 subunit from the cytosol into the nucleus, and then elevate the production of NO, TNF-α, IL-1β, IL-6 and MCP-1 by BV2 microglial cells. In a neuron-microglia co-culture system, BV2 microglia treated with LaCl3 resulted in a significant increase of the rates of neuron apoptosis. Conversely, the pre-treatment with PDTC (an inhibitor of the NF-κB signaling pathway) could inhibit the release of inflammatory cytokines and reduce the number of apoptotic neurons caused by La. These findings suggested that the neuron injury induced by LaCl3 might be related to the abnormal activation of microglia, which could remarkably increase the expression and release of pro-inflammatory cytokines via activating the NF-κB signaling pathway.