Abstract
Background Lanthanum (La) exposure can cause central nervous system (CNS) damage and dysfunction in children, seriously affecting intellectual development. miR-124 plays an important role in the development of the nervous system. We exposed rats to a La environment then observed the rats' learning and memory damage and neurotoxicity and the relationship with miR-124. Methods Rats were exposed to LaCl3 via drinking water. The rats' offspring were exposed to LaCl3 from their mother before weaning, then from La water for 28 days. A Morris water maze was used to observe spatial memory capabilities. H&E staining and TUNEL assays were used to observe pathological changes and apoptosis in the hippocampus. miR-124 was detected by RT-qPCR, and its targeting was confirmed by luciferase assay. The HT22 cell line was cultured with LaCl3 and treated with miR-124 mimics or inhibitors; then, expression of PI3K/Akt-related proteins was detected by western blot. Results La exposure can lead to impaired learning and memory ability in offspring. Offspring with La accumulations in the hippocampus showed severe damage, disordered cells, and increased neurocyte apoptosis. In vitro, the postsynaptic density protein 95 was downregulated under La exposure and apoptosis increased. This effect of La can be attenuated by miR-124 inhibitors and enhanced by miR-124 mimics. LaCl3 exposure increased miR-124 expression and targeting on PIK3CA, downregulating PI3K, p-Akt, and p-NF-κB p65. Conclusion La causes neurotoxicity by upregulating miR-124 expression and targeting PIK3CA through the PI3K/Akt signaling pathway.
Highlights
Rare earth elements (REEs) consist of 15 elements including lanthanum (La), scandium (Sc), and yttrium (Y), usually found in symbiotic forms in the external environment
Young animals can be exposed to REEs through breastfeeding, leading to damage and dysfunction of the central nervous system
We found that PIK3CA is one of the predicted target proteins of miR-124 and identified a 3′-UTR specific binding area between the sequence of PIK3CA and miR-124 (Figure 6(a))
Summary
Rare earth elements (REEs) consist of 15 elements including lanthanum (La), scandium (Sc), and yttrium (Y), usually found in symbiotic forms in the external environment. Young animals can be exposed to REEs through breastfeeding, leading to damage and dysfunction of the central nervous system. Lanthanum (La) exposure can cause central nervous system (CNS) damage and dysfunction in children, seriously affecting intellectual development. We exposed rats to a La environment observed the rats’ learning and memory damage and neurotoxicity and the relationship with miR-124. The postsynaptic density protein 95 was downregulated under La exposure and apoptosis increased. This effect of La can be attenuated by miR-124 inhibitors and enhanced by miR-124 mimics. LaCl3 exposure increased miR-124 expression and targeting on PIK3CA, downregulating PI3K, p-Akt, and p-NF-κB p65. La causes neurotoxicity by upregulating miR-124 expression and targeting PIK3CA through the PI3K/Akt signaling pathway
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