Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia.

Zechel JL, Gamboa JL, Peterson AG, Puchowicz MA, Selman WR, Lust WD
Birth Defects Res B Dev Reprod Toxicol. 2005 74 (4): 287-99

PMID: 16094620 · DOI:10.1002/bdrb.20051

BACKGROUND - Neonatal neurodevelopment is influenced by a variety of external factors, although the mechanisms responsible are poorly understood. Prenatal hypoxia, from physiological or chemical sources, can have no discernible effect, or can result in a broad spectrum of abnormalities.

METHODS - To mimic some of the maternal effects of smoking, we developed a model that investigates the effects of intermittent hypoxia (IH), with or without concurrent nicotine in timed pregnant Sprague-Dawley rats.

RESULTS - We found no significant differences between litter sizes or birthweight of pups from any treatment group, but animals exposed to IH (with or without nicotine) showed long term diminished body weights. Animals subjected to IH consistently showed a transient delay in neuronal migration early in the postpartum period, which was amplified by concurrent nicotine administration. We observed increased c-Abl protein levels in animals from the IH treatment groups. Multiple proteins involved in the intricate control of neuronal migration were also altered in response to this treatment, primarily the downstream targets of c-Abl: Cdk5, p25, and the cytoskeletal elements neurofilament H and F-actin and catalase. Catalase activity and protein levels, already elevated in response to IH, were further amplified by simultaneous nicotine exposure.

CONCLUSIONS - This new model provides a novel system for investigating the effects of low grade IH in the developing brain and suggests that concurrent nicotine further aggravates many of the deleterious effects of IH.

Copyright 2005 Wiley-Liss, Inc

MeSH Terms (20)

Actins Animals Animals, Newborn Body Weight Catalase Cell Movement Female Glutathione Peroxidase Hypoxia Immunoblotting Immunoprecipitation Maternal Exposure Neurons Nicotine Pregnancy Pregnancy, Animal Prenatal Exposure Delayed Effects Proto-Oncogene Proteins c-abl Rats Rats, Sprague-Dawley

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