A neurodevelopmental model of schizophrenia: Neonatal disconnection of the hippocampus
A neurodevelopmental model of schizophrenia: Neonatal disconnection of the hippocampus
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DOI：
10.1080/1029842021000022089
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发表时间：
2002-01-01
影响因子：
3.7
通讯作者：
Weinberger, Daniel R.
中科院分区：
文献类型：
--
作者：
Lipska, Barbara K.;Weinberger, Daniel R.
在我们目前对精神分裂症的认识背景下，精神障碍的启发式模型可能被用来检验基于新的生物学发现而发展的理论的合理性，探索精神分裂症现象的机制，并开发潜在的新治疗方法。在一系列研究中，我们已经证明了新生大鼠腹侧海马区的兴奋性毒性损伤可以作为一个启发式模型。该模型似乎模拟了精神分裂症的一系列神经生物学和行为特征，包括可能与海马体结构相互联系的关键大脑区域的功能病理，并以抗精神病药物-纹状体/伏隔核和前额皮质为靶点，并导致在青春期或成年早期出现一些与多巴胺相关的行为异常。此外，我们的数据显示，即使在发育的关键时期，VH的短暂失活也可能足以扰乱前额叶皮质(也许还有其他相互关联的晚成熟区域)的正常成熟，并引发类似于在患有永久性兴奋毒性损伤的动物身上观察到的行为变化。这些结果代表了一种潜在的新的精神分裂症方面的模式，而不是大体的解剖损伤。
In the context of our current knowledge about schizophrenia, heuristic models of psychiatric disorders may be used to test the plausibility of theories developed on the basis of new emerging biological findings, explore mechanisms of schizophrenia-like phenomena, and develop potential new treatments. In a series of studies, we have shown that neonatal excitotoxic lesions of the rat ventral hippocampus (VH) may serve as a heuristic model. The model appears to mimic a spectrum of neurobiological and behavioral features of schizophrenia, including functional pathology in presumably critical brain regions interconnected with the hippocampal formation and targeted by antipsychotic drugs-the striatum/nucleus accumbens and the prefrontal cortex, and leads in adolescence or early adulthood to the emergence of abnormalities in a number of dopamine related behaviors. Moreover, our data show that even transient inactivation of the VH during a critical period of development, that produces subtle, if any, anatomical changes in the hippocampus, may be sufficient to disrupt normal maturation of the prefrontal cortex (and perhaps, other interconnected late maturing regions) and trigger behavioral changes similar to those observed in animals with the permanent excitotoxic lesion. These results represent a potential new model of aspects of schizophrenia without a gross anatomical lesion.