Sub‐clinical carbon monoxide exposure inhibits developmental neuroapoptosis

Developmental neuroapoptosis (DN) occurs normally within CNS and is critical for synaptogenesis. Sub‐clinical carbon monoxide exposure (sCOe) occurs commonly in a variety of environments. The effects of postnatal sCOe on the developing brain are unknown. We hypothesize that sCOe inhibits DN resulting in disorders of learning and memory. CD‐1 mice underwent a 3‐hour exposure to 0 ppm, 5 ppm, or 100 ppm CO in air on postnatal day 10. Activated caspase‐3 decreased significantly in both the neocortex and hippocampus of CO exposed animals compared with air exposed controls. Brain caspase‐3 activity and TUNEL positive nuclei decreased in a dose dependent manner following sCOe. Cytochrome c significantly increased in mitochondria and decreased in cytosol following sCOe. One week after sCOe, NeuN and brain weight significantly increased. Four weeks after exposure, Morris water maze testing demonstrated CO cohorts had longer escape latency, spent less time in the target quadrant, and required more trials to reach the platform indicating impairments in reference memory, memory retention, and spatial working memory. These findings demonstrate that brief sCOe inhibits DN via inhibition of cytochrome c release, results in increased neuron number and brain size, and impairs learning and memory in a dose dependent manner. Thus, postnatal sCOe may be an important etiology of acquired neurocognitive impairment in children.