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Evaluation of Lead exposure's link to autism-like behavior and Shank 3 gene expression in C57BL/6J mice
Sunao Takaba1, Nelly Banda1, Rio Doya1
1Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
Insights
Maternal lead (Pb) exposure during pregnancy did not result in autism spectrum disorder (ASD)-like behaviors or altered Shank3 gene expression in male C57BL/6J mouse offspring. Further research is needed to explore dose-dependent and sex-specific effects.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Autism spectrum disorder (ASD) affects 1% of the global population, with unclear etiology.
- Environmental factors, including lead (Pb) exposure, are implicated in neurodevelopmental disorders.
- The developing brain is particularly vulnerable to neurotoxins like lead.
Purpose of the Study:
- To investigate the impact of maternal lead exposure on autism spectrum disorder-like behaviors in offspring.
- To assess the effects of perinatal lead exposure on Shank3 gene expression, a gene associated with ASD.
- To utilize a C57BL/6J mouse model to examine neurodevelopmental outcomes following maternal lead exposure.
Main Methods:
- Maternal C57BL/6J mice received 100 ppm lead acetate in drinking water during gestation and lactation.
- Offspring underwent behavioral testing (Social-Nonsocial interaction, Morris water maze) at 5 and 9 weeks.
- Lead levels were quantified (ICP-MS), and Shank3 gene expression was analyzed via real-time PCR.
Main Results:
- Lead concentrations were significantly elevated in offspring tissues (blood, brain, bone, liver, kidney), confirming maternal-fetal transfer.
- No significant differences in behavioral performance were observed between lead-exposed and control groups.
- Shank3 gene expression levels remained unchanged in lead-exposed offspring compared to controls.
Conclusions:
- Perinatal lead exposure at 100 ppm during the latter half of gestation did not induce measurable ASD-like phenotypes in male C57BL/6J mice.
- The tested dose and exposure window may not be sufficient to cause significant neurodevelopmental alterations related to ASD.
- Further investigation into dose-response relationships, sex differences, and molecular mechanisms is warranted.
Abstract:
Autism spectrum disorder (ASD) affects about 1 in 100 people worldwide, yet its causes remain poorly understood. Environmental factors, such as perinatal lead (Pb) exposure, have been linked to neurodevelopmental disruption, especially during periods when the blood-brain barrier is immature. This study aimed to assess ASD-like behavioral outcomes in offspring following maternal Pb exposure during neurodevelopment using a C57BL/6J mouse model. Pregnant dams received 100 ppm Pb acetate in their drinking water from the second week of gestation until weaning; controls were given deionised distilled water. Male offspring underwent behavioral assessments at 5 and 9 weeks of age using the three-chambered Social-Nonsocial (S-NS) interaction test and the Morris water maze. Pb concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), and real-time PCR was used to target Shank3, an ASD-associated gene. Lead concentrations were significantly elevated in the blood, brain, bone, liver, and kidney of exposed offspring, confirming effective maternal-foetal Pb transfer. However, no significant differences were observed between groups in behavioral performance or Shank3 expression. These findings suggest that perinatal Pb exposure at 100 ppm in the last trimester of pregnancy, under the conditions tested, does not induce measurable ASD-like phenotypes in male C57BL/6J mice. Further studies are warranted to investigate dose-dependent effects, sex-specific vulnerabilities, and the broader molecular pathways involved.
