Abstract
Carbon monoxide (CO) exposure at high concentrations results in overt neurotoxicity. Exposure to low CO concentrations occurs commonly yet is usually sub-clinical. Infants are uniquely vulnerable to a variety of toxins, however, the effects of postnatal sub-clinical CO exposure on the developing brain are unknown. Apoptosis occurs normally within the brain during development and is critical for synaptogenesis. Here we demonstrate that brief, postnatal sub-clinical CO exposure inhibits developmental neuroapoptosis resulting in impaired learning, memory, and social behavior. Three hour exposure to 5 ppm or 100 ppm CO impaired cytochrome c release, caspase-3 activation, and apoptosis in neocortex and hippocampus of 10 day old CD-1 mice. CO increased NeuN protein, neuronal numbers, and resulted in megalencephaly. CO-exposed mice demonstrated impaired memory and learning and reduced socialization following exposure. Thus, CO-mediated inhibition of neuroapoptosis might represent an important etiology of acquired neurocognitive impairment and behavioral disorders in children.
Highlights
Carbon monoxide (CO) is a colorless and odorless gas generated primarily as a by-product of incomplete combustion of hydrocarbons [1]
We demonstrate that brief, postnatal sub-clinical CO exposure inhibits developmental neuroapoptosis by impairing cytochrome c release from mitochondria, resulting in impaired learning and memory and social behavior. These results indicate that CO-mediated inhibition of neuroapoptosis might represent an important etiology of acquired neurocognitive impairment in children and could have important public health consequences
Resultant COHb levels were below the threshold that are known to elicit signs and symptoms in humans and were markedly less than values known to result in tissue hypoxia [4,5]
Summary
Carbon monoxide (CO) is a colorless and odorless gas generated primarily as a by-product of incomplete combustion of hydrocarbons [1]. Because the affinity of hemoglobin for CO is 240 times greater than that for oxygen, high COHb levels can impair tissue oxygen delivery by interfering with oxygen binding to and dissociation from hemoglobin [3,4]. Brief exposure to 220 ppm CO results in headache, dizziness, and impaired judgment while exposure to less than 120 ppm CO is usually sub-clinical [6]. Prenatal CO exposure has been shown to result in decreased birth weight, small infant head circumference, behavioral abnormalities, and disruption in cognitive function while chronic low concentration postnatal CO exposure has been shown to impair the developing rat auditory system [7,8,9]. The effects of brief postnatal sub-clinical CO exposure on the developing brain, are unknown
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