Gestational Exposure to Smog and Tension Altered Brain Connections in Male but Not Female Mice
Fifteen years ago, a young sailor named Carina Block was pregnant with her first child. Her demanding and stressful job overseas in the Navy regularly exposed her jet exhaust fumes. Carina gave birth to a healthy little girl. However, at the age of 4 months, Carina’s daughter, Madison, experienced life-threatening convulsions. At the hospital, her daughter was diagnosed with hydrocephalus, a fluid buildup in deep cavities of the brain. Due to Madison’s condition, the Navy sent Carina and her family to San Diego, where a pediatric neurosurgeon placed a shunt in her daughter’s brain to redirect the fluid to ease the increasing pressure. The procedure was a success, and today Madison is a thriving 14-year-old. Yet, when Madison was initially diagnosed, Carina began to wonder how her infant daughter developed hydrocephalus. Carina had a hunch that the jet fumes she breathed and the stress encountered at work while she was pregnant could have played a role in her daughter’s neurodevelopmental condition.
Fast forward to today, Carina is now a postdoctoral researcher at Duke University, and the lead author of a new study published in Cell Reports that examines the effects of prenatal environmental stressors on male offspring. Her latest research involved exposing pregnant mice to diesel exhaust and inducing stress in the animals by restricting their nest-building materials. These two environmental factors led to abnormal social behavior and lasting changes to the brains of mice’s male pups but not to the female offspring. Previously, the team that supported Carina in this study discovered that exposing pregnant mice to stress or air pollution alone did not affect how their offspring developed. But the current study shows that, synergistically, these two stressors led to an overabundance of connections between neurons (synapses) in male pups in a brain region that is heavily linked to making sense of social cues. In a normally functioning brain, synapses associated with successful behaviors are maintained and weak synapses are destroyed. Carina and her team suggest that the male offspring’s unusual social behavior could be connected to a lack of immune cells in the brain called microglia, which generally prune synapses in the brain. Interestingly, microglia can be influenced by inflammatory events in either the in utero environment or the postnatal environment.
Pinar Ayata, a neuroimmunology researcher at the Icahn School of Medicine at Mount Sinai, is excited by this research. She states, “The work highlights that environmental toxins and non-chemical stressors during pregnancy can have similar effects on brain development as severe infections. For the first time, we see a direct causality between external stressors in the womb, insufficient numbers of synapse-pruning microglia in a specific brain region, an associated abnormality in synapse numbers and brain activity, and shy behavior, similar to what’s seen in neurodevelopmental disorders.”
After conducting this research, Carina is now convinced that had Madison been a boy, that male infant would have developed autism. Carina and her co-authors hope that future research will find a molecular tag to help identify the synapse-pruning microglia so the cells can be tracked to see if they contract, expand, or even convert into other cell types. Furthermore, they would be thrilled to see a therapeutic way that could be developed to prevent microglia from being manipulated by environmental stressors.
