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- Title
Developmental Lead Exposure Alters Synaptogenesis through Inhibiting Canonical Wnt Pathway <i>In Vivo</i> and <i>In Vitro</i>.
- Authors
Hu, Fan; Xu, Li; Liu, Zhi-Hua; Ge, Meng-Meng; Ruan, Di-Yun; Wang, Hui-Li
- 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.
- Subjects
LEAD toxicology; SYNAPTOGENESIS; WNT proteins; NEUROPLASTICITY; HIPPOCAMPUS development; IN vitro studies
- Publication
PLoS ONE, 2014, Vol 9, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0101894