Neurodevelopmental consequences of sub-clinical carbon monoxide exposure in newborn mice

• Published in: PloS one Vol. 7; no. 2; p. e32029
• Main Authors: Cheng, Ying, Thomas, Adia, Mardini, Feras, Bianchi, Shannon L, Tang, Junxia X, Peng, Jun, Wei, Huafeng, Eckenhoff, Maryellen F, Eckenhoff, Roderic G, Levy, Richard J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.02.2012; Public Library of Science (PLoS)
• Subjects: Anesthesiology; Animals; Animals, Newborn; Apoptosis; Biology; Brain; Brain - drug effects; Brain - growth & development; Carbon monoxide; Carbon Monoxide - toxicity; Caspase; Caspase-3; Child development; Children; Children & youth; Cognition; Critical care; Cytochrome; Cytochrome c; Etiology; Exposure; Health sciences; Hippocampus; Hypoxia; Infants; Learning Disorders - chemically induced; Medicine; Megalencephaly; Memory; Memory Disorders - chemically induced; Mice; Mitochondria; Neocortex; Neurons; Neurotoxicity; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - physiopathology; Pain; Rodents; Social behavior; Social discrimination learning; Synaptogenesis; Toxins; Washington DC; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032029

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.