title: Neurodevelopmental consequences of sub-clinical carbon monoxide exposure in newborn mice.
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.
authors.affiliation: Division of Anesthesiology and Pain Medicine, Children's National Medical Center, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Adia
authors.initials: A
authors.lastname: Thomas
authors.forename: Feras
authors.initials: F
authors.lastname: Mardini
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Bianchi
authors.forename: Junxia X
authors.initials: JX
authors.lastname: Tang
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wei
authors.forename: Maryellen F
authors.initials: MF
authors.lastname: Eckenhoff
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Levy
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D002248:Carbon Monoxide / Q000633:toxicity*; D006624:Hippocampus; D007859:Learning Disabilities / Q000139:chemically induced*; D008569:Memory Disorders / Q000139:chemically induced*; D051379:Mice; D019579:Neocortex; D009474:Neurons; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000503:physiopathology
chemical_list: D002248:Carbon Monoxide