Neurotoxicity Research

, Volume 24, Issue 1, pp 80–93

Differential Responses of Hippocampal Neurons and Astrocytes to Nicotine and Hypoxia in the Fetal Guinea Pig

  • Tamara Blutstein
  • Michael A. Castello
  • Shaun S. Viechweg
  • Maria M. Hadjimarkou
  • Joseph A. McQuail
  • Mary Holder
  • Loren P. Thompson
  • Jessica A. Mong
Original Article


In utero exposure to cigarette smoke has severe consequences for the developing fetus, including increased risk of birth complications and behavioral and learning disabilities later in life. Evidence from animal models suggests that the cognitive deficits may be a consequence of in utero nicotine exposure in the brain during critical developmental periods. However, maternal smoking exposes the fetus to not only nicotine but also a hypoxic intrauterine environment. Thus, both nicotine and hypoxia are capable of initiating cellular cascades, leading to long-term changes in synaptic patterning that have the potential to affect cognitive functions. This study investigates the combined effect of in utero exposure to nicotine and hypoxia on neuronal and glial elements in the hippocampal CA1 field. Fetal guinea pigs were exposed in utero to normoxic or hypoxic conditions in the presence or absence of nicotine. Hypoxia increased the protein levels of matrix metalloproteinase-9 (MMP-9) and synaptophysin and decreased the neural density as measured by NeuN immunoreactivity (ir). Nicotine exposure had no effect on these neuronal parameters but dramatically increased the density of astrocytes immunopositive for glial fibrillary acidic protein (GFAP). Further investigation into the effects of in utero nicotine exposure revealed that both GFAP-ir and NeuN-ir in the CA1 field were significantly reduced in adulthood. Taken together, our data suggest that prenatal exposure to nicotine and hypoxia not only alters synaptic patterning acutely during fetal development, but that nicotine also has long-term consequences that are observed well into adulthood. Moreover, these effects most likely take place through distinct mechanisms.


Neuronal insult Synaptic patterning Matrix metalloproteinase Glial fibrillary acidic protein CNS development Smoking 


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Tamara Blutstein
    • 1
    • 2
    • 4
  • Michael A. Castello
    • 1
    • 5
  • Shaun S. Viechweg
    • 1
  • Maria M. Hadjimarkou
    • 1
  • Joseph A. McQuail
    • 1
  • Mary Holder
    • 1
  • Loren P. Thompson
    • 3
  • Jessica A. Mong
    • 1
    • 2
  1. 1.Department of PharmacologyUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Program in NeuroscienceUniversity of Maryland School of MedicineBaltimoreUSA
  3. 3.Department of Obstetrics, Gynecology, and Reproductive SciencesUniversity of Maryland School of MedicineBaltimoreUSA
  4. 4.Department of NeuroscienceTufts University School of MedicineBostonUSA
  5. 5.School of Medicine, Loma Linda UniversityLoma LindaUSA

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