Increased cell proliferation in the rat anterior cingulate cortex following neonatal hypoxia: relevance to schizophrenia.
As a consequence of obstetric complications, neonatal hypoxia has been discussed as an environmental factor in the pathophysiology of schizophrenia. However, the biological consequences of hypoxia are unclear. The neurodevelopmental hypothesis of schizophrenia suggests that the onset of abnormal brain development and neuropathology occurs perinatally, whereas symptoms of the disease appear in early adulthood. In our animal model of chronic neonatal hypoxia, we have detected behavioral alterations resembling those known from schizophrenia. Disturbances in cell proliferation possibly contribute to the pathophysiology of this disease. In the present study, we used postnatal rats to investigate cell proliferation in several brain areas following neonatal hypoxia. Rats were repeatedly exposed to hypoxia (89 % N(2), 11 % O(2)) from postnatal day (PD) 4-8. We then evaluated cell proliferation on PD 13 and 39, respectively. These investigations were performed in the anterior cingulate cortex (ACC), caudate-putamen (CPU), dentate gyrus, and subventricular zone. Rats exposed to hypoxia exhibited increased cell proliferation in the ACC at PD 13, normalizing at PD 39. In other brain regions, no alterations have been detected. Additionally, hypoxia-treated rats showed decreased CPU volume at PD 13. The results of the present study on the one hand support the assumption of chronic hypoxia influencing transient cell proliferation in the ACC, and on the other hand reveal normalization during ageing.
Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Evelin L
EL
Schaeffer
Franziska
F
Kühn
Angelika
A
Schmitt
Wagner F
WF
Gattaz
Oliver
O
Gruber
Thomas
T
Schneider-Axmann
Peter
P
Falkai
Andrea
A
Schmitt
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006179:Gyrus Cinguli / Q000254:growth & development / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001973:Bromodeoxyuridine