Developmental Lead Exposure Alters Synaptogenesis through Inhibiting Canonical Wnt Pathway In Vivo and In Vitro
Open accessAbstract
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.
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Developmental BPA exposure in cultured hypothalamic cells causes a decrease of synapsin I phosphorylation.
“developmental BPA exposure in cultured hypothalamic cells causes decrease of synapsin I phosphorylation,33”
From Bisphenol A Impairs Synaptic Plasticity by Both Pre‐ and Postsynaptic Mechanisms (2017) · cites this paper as [33]
The Neuronal cultures and Western blotting assay sections describe lead-treated hippocampal neurons and measurement of β-catenin phosphorylation, not BPA-treated hypothalamic cells or synapsin I phosphorylation. Searches for BPA, hypothalamic cells, and synapsin phosphorylation found no passage addressing the attributed claim. (LLM, conf=0.78)
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- Authors
- Hu, F., Xu, L., Liu, Z.-H., Ge, M.-M., Ruan, D.-Y., & Wang, H.-L.
- Affiliations
- Hefei University of Technology (CN)
- University of Science and Technology of China (CN)
- Corresponding author
- Wang, Hui-Li
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-07-07
- Volume
- 9
- Issue
- 7
- Pages
- e101894
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4084981
- OpenAlex
- W2037265981
- Cited by
- 54
- References
- 56
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 5 · 2015: 6
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (973 Program, 21307024, 31200851)
- China Postdoctoral Science Foundation (2013M531500)
- Ministry of Education, India
- Program for New Century Excellent Talents in University (NCET-12-0835)
- National Key Research and Development Program of China (2012CB525003)
- Specialized Research Fund for the Doctoral Program of Higher Education of China (20130111110024)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- lead exposure, developmental neurotoxicity, synaptogenesis, dendritic spine formation, Wnt/β-catenin signaling, Wnt7a, β-catenin, hippocampal CA1, hippocampal pyramidal neurons, synaptic plasticity, lead acetate, lactation period, Golgi-Cox staining
- MeSH terms
- Animals, Embryo, Mammalian, Hippocampus, Humans, Lead, Neurotoxins, Synapses, Time Factors, Rats, Sprague-Dawley, Pyramidal Cells, Dendritic Spines, Wnt Proteins, Rats, HEK293 Cells, Wnt Signaling Pathway
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