title: Developmental lead exposure alters synaptogenesis through inhibiting canonical Wnt pathway in vivo and in vitro.
abstract: Lead (Pb) exposure has been implicated in the impairment of synaptic plasticity in the developing hippocampus, but the mechanism remains unclear. Here, we investigated whether developmental lead exposure affects the dendritic spine formation through Wnt signaling pathway in vivo and in vitro. Sprague-Dawley rats were exposed to lead throughout the lactation period and Golgi-Cox staining method was used to examine the spine density of pyramidal neurons in the hippocampal CA1 area of rats. We found that lead exposure significantly decreased the spine density in both 14 and 21 days-old pups, accompanied by a significant age-dependent decline of the Wnt7a expression and stability of its downstream protein (β-catenin). Furthermore, in cultured hippocampal neurons, lead (0.1 and 1 µM lead acetate) significantly decreased the spine density in a dose-dependent manner. Exogenous Wnt7a application attenuated the decrease of spine density and increased the stability of the downstream molecules in Wnt signaling pathway. Together, our results suggest that lead has a negative impact on spine outgrowth in the developing hippocampus through altering the canonical Wnt pathway.
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Hu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Ge
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Di-Yun
authors.initials: DY
authors.lastname: Ruan
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui, China.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D006801:Humans; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D009498:Neurotoxins; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D007854:Lead