Maternal exposures to alcohol and nicotine, which are sometimes abused during pregnancies, are linked to fetal growth retardation and neurotoxicity. However, the individual and combined effects of the toxins on molecular mechanisms of fetal development are poorly understood.
Kirill Larin, professor and director of the biomedical engineering graduate program at the UH Cullen College of Engineering, earned a five-year, $2 million Research Project Grant (R01) from the National Institutes of Health (NIH) to explore molecular pathways involved with brain development during both chronic and occasional exposure to nicotine and alcohol, both separately and combined.
Larin and his collaborator, Rajesh Miranda, professor of neuroscience and experimental therapeutics at Texas A&M Health Science Center in Bryan, are exploring the interplay between the two toxins on embryonic brain development in mice using optical coherence tomography (OCT), a novel high-resolution mouse embryonic brain imaging and analysis approach.
“We have pioneered OCT-based methodology for live in utero imaging and longitudinal phenotypic analysis of mouse fetuses,” Larin said. “We propose to further develop both the technology and the methodology for longitudinal brain imaging and analysis.”
Larin and Miranda are investigating whether the toxins have antagonistic, synergetic or a combination of those effects on brain development in live mouse embryos. Their study focuses on the second trimester–equivalent period of development when the neuronal stem cells give rise to most of the neurons of the adult brain.
During the course of this project, they plan to establish a live mouse embryonic brain imaging approach, to develop a set of protocols and detailed assessments to quantitatively characterize dynamic embryonic brain development with cellular resolution, and to investigate whether ethanol and nicotine synergize to disrupt brain development or exhibit partially antagonistic effects. Furthermore, they intend to explore the feasibility of using nicotinic receptor antagonists and agonists to prevent the individual and combined effects of the toxins.
“Studying these effects is highly significant from both fundamental biology and teratogenic points of view since it may have particular significant impact for the development of novel and innovative therapies for reversing teratology,” Larin said.