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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Low-level lead exposure triggers neuronal apoptosis in the developing mouse brain
William H Dribben1, Catherine E Creeley, Nuri Farber
1Division of Emergency Medicine, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8072, St. Louis, MO 63110, USA. dribbenw@wustl.edu
Neurotoxicology and Teratology
|June 7, 2011
Summary
Lead exposure in neonatal mice caused significant brain cell death (apoptosis) on postnatal day 7, highlighting risks to the developing nervous system. This finding underscores the neurotoxic potential of lead in young children.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Lead toxicity is a persistent public health issue, especially in young children.
- Lead acts as a potent N-methyl-D-aspartate (NMDA) antagonist.
- NMDA antagonist exposure during early brain development can cause apoptotic neurodegeneration.
Purpose of the Study:
- To assess the ability of lead exposure to induce apoptosis in the neonatal mouse brain.
- To investigate the neurotoxic effects of lead during critical developmental periods.
Main Methods:
- Neonatal mice received lead injections (350 mg/kg) on postnatal day 7 or 14.
- Histological analyses included activated caspase-3 immunohistochemistry, De Olmos silver technique, Nissl staining, and electron microscopy.
- Neurodegeneration was evaluated 8-24 hours post-treatment.
Main Results:
- Lead exposure caused significant neurodegeneration in multiple brain regions, including the caudate/putamen, hippocampus, subiculum, and frontal cortex.
- Ultrastructural examination confirmed cellular profiles indicative of apoptotic cell death.
- Increased apoptotic neurodegeneration was observed in mice treated on postnatal day 7, but not on day 14.
Conclusions:
- Neonatal lead exposure can induce significant apoptotic neurodegeneration in the developing mouse brain.
- The immature nervous system exhibits heightened susceptibility to lead-induced neurotoxicity, particularly around postnatal day 7.
- These findings contribute to understanding the mechanisms of lead's neurotoxic effects on the developing brain.
