by Tomoyasu Wakuda, Hideo Matsuzaki, Katsuaki Suzuki, Yasuhide Iwata, Chie Shinmura, Shiro Suda, Keiko Iwata, Shigeyuki Yamamoto, Genichi Sugihara, Kenji J. Tsuchiya, Takatoshi Ueki, Kazuhiko Nakamura, Daiichiro Nakahara, Nori Takei, Norio Mori

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.