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

Abstract

Abstract By observing the changes in hippocampal nerve cell damage in offspring rats exposed to different doses of lanthanum chloride (LaCl3), the role of TNFR-RIPK1/RIPK3 necroptosis pathway in La-mediated neurotoxicity was explored. At 49 days after the birth of the LaCl3-exposed offspring rats, neurobehavioural tests were performed to assess the spatial learning and memory; the ultrastructure of hippocampal tissues of the offspring rats was observed by electron microscopy; the number of Nissl bodies in hippocampal tissue was evaluated by Nissl staining; and the protein contents of TNFR-RIPK1/RIPK3 signalling pathway in hippocampal tissue were measured by Western blotting. The learning and memory ability of the offspring decreased after LaCl3 exposure. Nissl staining showed that in the lanthanum-exposed rats, Nissl body number in the hippocampus was significantly decreased, and the cell arrangement was disordered. The ultramicroscopic structure of hippocampal neurons in lanthanum-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. Western blotting proved that the contents of TNFR1, P-RIPK1, P-RIPK3 and P-MLKL in hippocampal neurons increased significantly as the LaCl3 dose increased. Lanthanum exposure retarded the growth and development of rat offspring ,impaired spatial learning and memory, and induced mitochondrial damage in hippocampal neurons, resulting in cellular necroptosis .These changes may be related to abnormal expression of TNFR-RIPK1/RIPK3 signaling pathway-related molecules.