Role of Wnt/β-catenin signaling in the protective effect of epigallocatechin-3-gallate on lead-induced impairments of spine formation in the hippocampus of rats

The Wnt/β-catenin signaling pathway has been implicated in the development of dendritic spines, which are the structural basis for the induction of long-term potentiation. We have previously shown that exposure to Pb during development causes damage to the spines on hippocampal pyramidal neurons by decreasing the activity of the Wnt/β-catenin signaling pathway. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, has been shown to recover impaired hippocampal-dependent long-term potentiation in rats exposed to Pb. We report here an investigation of whether this protective function of EGCG works by regulating the Wnt/β-catenin signaling pathway to refine the formation of spines in rats exposed to Pb during development. Sprague-Dawley rat pups were exposed to Pb from parturition to weaning and EGCG (10, 25 and 50 mg kg−1) was given intraperitoneally from postnatal day 14 to postnatal day 21. We found that exposure to Pb significantly decreased the density of dendritic spines and spine head size of pyramidal neurons in the hippocampal CA1 areas; EGCG (10 and 25 mg kg−1) reversed this Pb-induced spine damage. EGCG (10 and 25 mg kg−1) also recovered the expression of Wnt7a and β-catenin phosphorylation after exposure to Pb. However, 50 mg kg−1 of EGCG did not restore the spine morphology and the activity of the Wnt/β-catenin pathway on rats exposed to Pb. EGCG did not exert any protective effect on Pb2+-induced damage in cultured hippocampal neurons when Wnt7a shRNA applied. Our results show that EGCG (within a certain dose range) has a significant protective effect on spine formation and maturation through Wnt/β-catenin signaling in young rats exposed to Pb. This effect involves the up-regulation of Wnt7a expression and the attenuation of phospho-β-catenin expression. EGCG may be a potential complementary agent in the treatment of Pb poisoning.