Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
J Neural Transm (Vienna). 2013 Jan;120(1):187-95. doi: 10.1007/s00702-012-0859-y. Epub 2012 Jul 19.
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.
由于产科并发症，新生儿缺氧已被讨论为精神分裂症病理生理学中的环境因素。然而，缺氧的生物学后果尚不清楚。精神分裂症的神经发育假说表明，异常大脑发育和神经病理学的开始发生在围产期，而疾病的症状出现在成年早期。在我们的慢性新生儿缺氧动物模型中，我们检测到了类似于精神分裂症的行为改变。细胞增殖的紊乱可能有助于这种疾病的病理生理学。在本研究中，我们使用新生大鼠来研究新生儿缺氧后几个脑区的细胞增殖。从出生后第 4-8 天，大鼠反复暴露于缺氧（89%N2，11%O2）中。然后，我们分别在 PD13 和 PD39 评估细胞增殖。这些研究在扣带回前部皮层（ACC）、尾壳核（CPU）、齿状回和侧脑室下区进行。暴露于缺氧的大鼠在 PD13 时表现出 ACC 中的细胞增殖增加，在 PD39 时恢复正常。在其他脑区，未检测到变化。此外，缺氧处理的大鼠在 PD13 时表现出 CPU 体积减小。本研究的结果一方面支持慢性缺氧影响 ACC 中短暂细胞增殖的假设，另一方面揭示了在老化过程中的正常化。
