Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity

Area of Science:

• Environmental toxicology
• Neuroscience
• Bioinformatics

Background:

• Thousands of environmental chemicals pose risks to neurodevelopment.
• Neurodevelopment involves critical plasticity periods sensitive to chemical disruption.
• Systematic evaluation of neurotoxicants is urgently needed.

Purpose of the Study:

• To identify environmental chemicals that disrupt critical periods of neurodevelopmental plasticity.
• To demonstrate a novel bioinformatics approach for assessing neurotoxicant impacts.

Main Methods:

• An integrative bioinformatics approach was applied to public data.
• 214 human neurotoxicants were analyzed for disruption of a transcriptional signature of brain plasticity.
• Lead (Pb) was identified as a critical period neurotoxicant.

Main Results:

• Dozens of neurotoxicant signatures disrupting critical period plasticity were identified.
• Lead (Pb) was confirmed in vivo to partially suppress critical period plasticity.
• Exposure timing analogous to autism-associated exposure was used.

Conclusions:

• A novel bioinformatics approach can systematically identify neurotoxicants affecting childhood neurodevelopment.
• Lead (Pb) is a critical period neurotoxicant with potential implications for neurodevelopmental disorders.
• This method can be extended to assess other environmental chemicals.