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Abstract
Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.
To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) via whole-body inhalation at gestational day (GD) 10 or GD20. Control animals received a sham FA at both time points. Brain tissue was collected at gestational day GD21 following GD10 or GD20 ozone exposure. Fetal brains were processed with unbiased, quantitative mass spectrometry to identify altered protein abundance and posttranslational states in Ingenuity Pathway Analysis, and results were further interrogated with immunohistochemistry (IHC).
Key processes to neurodevelopment distinctly altered with GD10 versus GD20 exposure were a predicted increase in apoptosis (enrichment p-value = 0.0018; prediction z-score = 2.541) and a decrease in neuritogenesis (enrichment p-value = 0.00128; prediction z-score = -2.494). IHC for Cytochrome C, active Caspase 3, and mitochondria investigated altered apoptosis by the intrinsic pathway while GAP43 (growth cone marker), MAP2 (dendritic marker), and Nestin (neural progenitor cell marker) antibodies probed for neuritogenesis.
Results demonstrate a time-dependent gestational effect on neurodevelopmental vulnerability in fetal brain proteome and changes to cell proliferation-migration and circuit formation following O3 exposure. IHC results suggest acute apoptosis from ozone exposure decreases neuronal outbranching. Hence, cognitive and behavioral childhood performance issues like ADHD, memory deficiencies, motor impairments may be attributed to gestational ozone exposure which disproportionately affects urban children.
Publication Date
2024
Subject Major(s)
Anatomy and Neurobiology
Keywords
Neurodevelopment, ozone, gestation, apoptosis, neuritogenesis, reactive oxygen species, fetal vulnerability during pregnancy, acute/subacute exposure, Cytochrome C, Caspase 3, mitochondrial markers, GAP43, MAP2, Nestin
Disciplines
Biochemistry | Developmental Biology | Developmental Neuroscience | Disorders of Environmental Origin | Nervous System Diseases | Toxicology
Current Academic Year
Sophomore
Faculty Advisor/Mentor
Dr. Andrew Ottens
Faculty Advisor/Mentor
Sarah Brent
Rights
© The Author(s)
Included in
Biochemistry Commons, Developmental Biology Commons, Developmental Neuroscience Commons, Disorders of Environmental Origin Commons, Nervous System Diseases Commons, Toxicology Commons