Alterations of Synaptic Proteins in the Hippocampus of Mouse Offspring Induced by Developmental Lead Exposure
- 401 Downloads
Lead exposure can cause cognitive dysfunction in children, thus it still raises important public health concerns in China and other countries. However, the underlying molecular mechanisms are still not well defined. In this study, we aimed to elucidate the mechanisms underlying lead neurotoxicity by focusing on alterations of synaptic proteins in the mouse hippocampus at the early life. Mother mice and their offspring were exposed to 0, 0.5, 1.0, and 2.0 g/L lead via drinking water from the first day of gestation until postnatal day (PND) 40. Synaptic ultrastructure and expressions of postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS) and synaptophysin (SYP) at both protein and gene levels in the hippocampus were analyzed. The results revealed that developmental lead exposure caused a diminished postsynaptic density in the hippocampus. Moreover, the protein levels of PSD-95, nNOS, and SYP decreased significantly due to developmental lead exposure. On the other hand, the messenger RNA (mRNA) levels of PSD-95 and SYP decreased significantly in PND 40 mice exposed to lead. Collectively, developmental lead exposure might result in decreased protein and gene expressions of both presynaptic and postsynaptic proteins. Our findings raised a possibility that alterations of synaptic proteins in the hippocampus induced by lead exposure at the early life might serve an important role for the subsequent intellectual impairments, e.g., deficits in spatial learning and memory ability at later ages shown in our recently published paper.
KeywordsDevelopmental lead exposure Mice Synaptic proteins Postsynaptic density protein-95 (PSD-95) Neuronal nitric oxide synthase (nNOS) Synaptophysin (SYP)
This work was supported by The National Natural Science Foundation of China (no. 31070992), Program for Liaoning Innovative Research Team in University (LT2015028), Liaoning Provincial Natural Science Foundation (no. 20102263), and Science and Technology Plan Project of Educational Department of Liaoning Province (no. L2010559).
Compliance with Ethical Standards
Conflict of Interest
The authors declared no competing interests.
- 13.Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RG, Morrison JH, O’Dell TJ, Grant SG (1998) Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396(6710):433–439CrossRefPubMedGoogle Scholar
- 34.Kellom M, Basselin M, Keleshian VL, Chen M, Rapoport SI, Rao JS (2012) Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation. BMC Neurosci 13:50CrossRefPubMedPubMedCentralGoogle Scholar