Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine-induced hyperlocomotion in adulthood.
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.
Wakuda
Tomoyasu
T
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Matsuzaki
Hideo
H
Suzuki
Katsuaki
K
Iwata
Yasuhide
Y
Shinmura
Chie
C
Suda
Shiro
S
Iwata
Keiko
K
Yamamoto
Shigeyuki
S
Sugihara
Genichi
G
Tsuchiya
Kenji J
KJ
Ueki
Takatoshi
T
Nakamura
Kazuhiko
K
Nakahara
Daiichiro
D
Takei
Nori
N
Mori
Norio
N
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
D000697:Central Nervous System Stimulants; D008694:Methamphetamine