Prenatal e-cigarette exposure induces region- and cell type-specific metabolic and developmental reprogramming

Area of Science:

• Neuroscience
• Developmental Biology
• Toxicology

Background:

• Prenatal e-cigarette exposure (PeCE) is a growing concern.
• Adverse neurodevelopmental outcomes are linked to PeCE.
• Mechanisms of maternal vaping's impact on early brain development are unclear.

Purpose of the Study:

• To investigate the effects of PeCE on neonatal rat brain development at regional and cellular levels.
• To identify molecular pathways disrupted by maternal vaping.
• To link PeCE to neurodevelopmental disease risk.

Main Methods:

• Integrated spatial transcriptomics, single-nucleus RNA sequencing (snRNA-seq), and lipidomics.
• Analyzed neonatal rat brain responses to PeCE.
• Examined regional and cellular vulnerability.

Main Results:

• PeCE caused significant spatial heterogeneity in brain vulnerability, with the striatum most affected.
• Disrupted lipid metabolic homeostasis and altered Ca2+ signaling were observed.
• PeCE induced region-specific synaptic stress, delayed neuron maturation, and suppressed dendritic spine development.

Conclusions:

• Disrupted metabolic and developmental reprogramming is key to neonatal brain vulnerability from maternal vaping.
• PeCE-sensitive genes overlap with human neurodevelopmental and autism spectrum disorder risk loci.
• Provides a mechanistic link between PeCE and neurodevelopmental disease risk.