Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia

Jennifer L. Zechel, Jorge L. Gamboa, Allyn G. Peterson, Michelle Puchowicz, Warren R. Selman, W. David Lust

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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. We also describe IH as a previously unreported mechanism for c-Abl expression.

Original languageEnglish (US)
Pages (from-to)287-299
Number of pages13
JournalBirth Defects Research Part B - Developmental and Reproductive Toxicology
Volume74
Issue number4
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Nicotine
Animals
Catalase
Proto-Oncogene Proteins c-abl
Rats
Actins
Brain
Proteins
Hypoxia
Litter Size
Intermediate Filaments
Postpartum Period
Sprague Dawley Rats
Smoking
Body Weight

All Science Journal Classification (ASJC) codes

  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis

Cite this

Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia. / Zechel, Jennifer L.; Gamboa, Jorge L.; Peterson, Allyn G.; Puchowicz, Michelle; Selman, Warren R.; Lust, W. David.

In: Birth Defects Research Part B - Developmental and Reproductive Toxicology, Vol. 74, No. 4, 01.08.2005, p. 287-299.

Research output: Contribution to journalArticle

Zechel, Jennifer L. ; Gamboa, Jorge L. ; Peterson, Allyn G. ; Puchowicz, Michelle ; Selman, Warren R. ; Lust, W. David. / Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia. In: Birth Defects Research Part B - Developmental and Reproductive Toxicology. 2005 ; Vol. 74, No. 4. pp. 287-299.
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