CELL BIOLOGY OF MODELS FOR HUMAN BRAIN DISORDERS

节段性小鼠(Ts65Dn)是人类唐氏综合征(21三体)的动物模型。只有与人类21号染色体同源的16号染色体片段才是三体。成年Ts65Dn小鼠在空间任务上表现出异常学习。我们发现，从这只小鼠分离的海马体也表现出异常的长时程增强(LTP)和长时程增强(LTD)，这是学习和记忆的模型。然而，Western blotting估计NMDA受体主要亚单位(NR1)和α-1C钙通道亚单位蛋白的表达并不异常。此外，使用体内1H磁共振波谱，我们证明了Ts65Dn小鼠大脑中肌醇的水平与对照小鼠相比增加，这与我们先前证明唐氏综合症患者大脑中的肌醇增加是一致的。因此，异常的磷脂酰肌醇信号可能有助于唐氏综合征患者的智力低下，并可以在适当的小鼠模型中进行研究。海人藻酸受体介导的兴奋性突触后电流发生在脊髓，并参与伤害性感受。我们作为止痛药开发的新型非NMDA拮抗剂被证明干扰红藻氨酸对大鼠脊髓的作用。-红藻氨酸，长期增强，长期抑郁，海马体，唐氏综合征，三体65Dn小鼠

The segmental trisomy mouse (Ts65Dn) is an animal model of human Down syndrome (trisomy 21). It is trisomic only for the segment of chromosome 16 that is homologous to human chromosome 21. The adult Ts65Dn mouse demonstrates abnormal learning on spatial tasks. We found that the isolated hippocampus from this mouse also demonstrates abnormal long-term potentiation (LTP) and long term depression (LTD), models for learning and memory. Expression of the NMDA receptor main subunit (NR1) and of the alpha-1C Ca2+ channel subunit proteins, estimated by Western blotting, was not abnormal, however. Additionally, using in vivo 1H magnetic resonance spectroscopy we demonstrated an increased level of myoinositol in brains of Ts65Dn compared with control mice, consistent with our prior demonstration of increased myoinositol in brains of Down syndrome subjects. Thus, abnormal phosphoinositide signaling may contribute to mental retardation in Down syndrome, and can be examined in an appropriate mouse model. Kainate receptor-mediated excitatory postsynaptic currents occur in the spinal cord and are involved in nociception. Novel non-NMDA antagonists that we developed as anti-pain medication were shown to interfere with the effect of kainate in the rat spinal cord. - Kainate, Long-term potentiation, Long-term depression, Hippocampus, Down syndrome, Trisomy 65Dn mouse