The TNFR-RIPK1/RIPK3 signalling pathway mediates the effect of lanthanum on necroptosis of nerve cells

TL;DR

Lanthanum exposure in rats causes nerve cell damage and memory issues by activating a specific cell death pathway.

Contribution

This study identifies the TNFR-RIPK1/RIPK3 signaling pathway as a mediator of lanthanum-induced necroptosis in nerve cells.

Findings

Lanthanum exposure reduces Nissl bodies and disrupts hippocampal cell structure in rats.

Lanthanum increases mitochondrial abnormalities and activates necroptosis markers in hippocampal neurons.

Higher LaCl3 doses correlate with increased expression of TNFR1, P-RIPK1, P-RIPK3, and P-MLKL proteins.

Abstract

Lanthanum (La) accumulates resulted in detrimental alterations in the morphology and structure of hippocampal neurons, but the specific mechanism remains unclear. At 49 days after the birth of LaCl3-exposed offspring rats, number of Nissl bodies and the neural cell structure in hippocampal tissue was evaluated by Nissl and HE staining; the ultrastructure of hippocampal CA1 zone was observed by electron microscopy. Learning and memory ability of the offspring decreased after LaCl3 exposure. Nissl staining showed that in the La-exposed rats, Nissl body number in the hippocampus was significantly decreased, and the cell arrangement was disordered. The ultramicroscopic structure of hippocampal neurons in La-exposed rats showed that the mitochondrial volume was increased; ridges were shorter, decreased in number, and marginally shifted; and the matrix electron density was also decreased. The contents of TNFR1, P-RIPK1, P-RIPK3, and P-MLKL in hippocampal neurons increased significantly as the LaCl3 dose increased. La exposure retarded the growth and development of offspring rat, resulted hippocampal nerve cell necroptosis, and impaired spatial learning and memory, which related to abnormal expression of TNFR-RIPK1/RIPK3 pathway.

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