Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2008;3(11):e3648. doi: 10.1371/journal.pone.0003648. Epub 2008 Nov 5.

Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine-induced hyperlocomotion in adulthood.

Author information

  • 1Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.

Abstract

BACKGROUND:

Obstetric complications have been regarded as a risk factor for schizophrenia later in life. One of the mechanisms underlying the association is postulated to be a hypoxic process in the brain in the offspring around the time of birth. Hippocampus is one of the brain regions implicated in the late-onset dopaminergic dysfunction associated with hypoxic obstetric complications.

METHODOLOGY/PRINCIPAL FINDINGS:

We used an animal model of perinatal asphyxia, in which rat pups were exposed to 15 min of intrauterine anoxia during Cesarean section birth. At 6 and 12 weeks after birth, the behavior of the pups was assessed using a methamphetamine-induced locomotion test. In addition, the histopathology of the hippocampus was examined by means of stereology. At 6 weeks, there was no change in the methamphetamine-induced locomotion. However, at 12 weeks of age, we found an elevation in methamphetamine-induced locomotor activity, which was associated with an increase of dopamine release in the nucleus accumbens. At the same age, we also found a reduction of the dentate granule cells of the hippocampus.

CONCLUSIONS/SIGNIFICANCE:

These results suggest that the dopaminergic dysregulation after perinatal asphyxia is associated with a reduction in hippocampal dentate granule cells, and this may partly contribute to the pathogenesis of schizophrenia.

PMID:
18985150
[PubMed - indexed for MEDLINE]
PMCID:
PMC2572851
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk