Dietz David M, Pletnikov Mikhail V
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD 21205, USA.
Physiol Behav. 2003 Nov;80(2-3):359-66. doi: 10.1016/j.physbeh.2003.08.011.
Neonatal Borna disease virus (BDV) infection of the rat's brain produces neurodevelopmental damage similar to some pathological and clinical features of human developmental disorders, e.g., autism and schizophrenia. Since BDV-infected rats exhibited an inhibition of postnatal weight gain, the present study sought to evaluate a contribution of nutritional status to virus-induced neurodevelopmental injury. We compared neuroanatomical, neurochemical, and behavioral alterations following neonatal BDV infection and rearing in the oversized litters in Fischer344 rats on postnatal day (PND) 26. Despite a comparable weight gain inhibition, different patterns of brain pathology, alterations in brain monoamine systems, and behavioral deficits were observed in the BDV-infected rats compared to the malnourished rats. While no appreciable cell injury was noted in the brains of the malnourished rats, a significant loss of Purkinje cells (PC) and early signs of degeneration of the hippocampal dentate gyrus were found in the BDV-infected rats. Both neonatal BDV infection and postnatal malnourishment increased tissue concentrations of serotonin [5-hydroxytryptamine (5-HT)] in the hippocampus. In contrast, increased turnover of 5-HT in the cortex and hippocampus and elevated turnover of dopamine (DA) in the striatum were found in the malnourished rats only, suggesting that different pathogenic mechanisms might underlie monoamine disturbances in virus-infected and malnourished rats. The observed dissimilar neuroanatomical and neurochemical abnormalities might explain the different responses to novelty in the BDV-infected and malnourished rats. Compared to the control rats, the BDV-infected rats exhibited novelty-induced hyperactivity, while no differences in locomotion were noted between the control and malnourished rats. Taken together, the present data indicate that virus-associated inhibition of postnatal weight gain is unlikely to account for the major BDV-associated neurodevelopmental alterations that seem to be due to specific effects of neonatal BDV infection.
新生大鼠脑部的博尔纳病病毒（BDV）感染会导致神经发育损伤，其病理和临床特征与人类发育障碍（如自闭症和精神分裂症）的某些特征相似。由于感染BDV的大鼠出生后体重增加受到抑制，本研究旨在评估营养状况对病毒诱导的神经发育损伤的影响。我们比较了出生后第26天（PND 26）在超大窝中饲养的新生BDV感染Fischer344大鼠的神经解剖学、神经化学和行为改变。尽管体重增加抑制程度相当，但与营养不良的大鼠相比，感染BDV的大鼠出现了不同模式的脑病理学改变、脑单胺系统改变和行为缺陷。营养不良的大鼠大脑中未观察到明显的细胞损伤，而感染BDV的大鼠中发现浦肯野细胞（PC）显著丢失以及海马齿状回早期退化迹象。新生BDV感染和出生后营养不良均会增加海马中血清素[5-羟色胺（5-HT）]的组织浓度。相比之下，仅在营养不良的大鼠中发现皮质和海马中5-HT的周转率增加以及纹状体中多巴胺（DA）的周转率升高，这表明病毒感染和营养不良的大鼠中，单胺紊乱可能存在不同的致病机制。观察到的不同神经解剖学和神经化学异常可能解释了感染BDV和营养不良的大鼠对新奇事物的不同反应。与对照大鼠相比，感染BDV的大鼠表现出新奇诱导的多动，而对照大鼠和营养不良的大鼠之间在运动方面未观察到差异。综上所述，目前的数据表明，病毒相关的出生后体重增加抑制不太可能是BDV相关主要神经发育改变的原因，这些改变似乎是由新生BDV感染的特定影响所致。
