title: Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine-induced hyperlocomotion in adulthood.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Wakuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Chie
authors.initials: C
authors.lastname: Shinmura
authors.forename: Shiro
authors.initials: S
authors.lastname: Suda
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Genichi
authors.initials: G
authors.lastname: Sugihara
authors.forename: Kenji J
authors.initials: KJ
authors.lastname: Tsuchiya
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Ueki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Nakahara
authors.forename: Nori
authors.initials: N
authors.lastname: Takei
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology / Q000662:veterinary; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D000697:Central Nervous System Stimulants; D002529:Cerebellar Nuclei / Q000473:pathology*; D002585:Cesarean Section / Q000009:adverse effects; D005260:Female; D006948:Hyperkinesis / Q000139:chemically induced* / Q000473:pathology*; D008694:Methamphetamine; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D007744:Obstetric Labor Complications / Q000473:pathology* / Q000503:physiopathology / Q000662:veterinary; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine