CELL BIOLOGY OF MODELS FOR HUMAN BRAIN DISORDERS

部分三体小鼠（Ts65Dn）是人类唐氏综合症（21三体）的动物模型。只有与人类21号染色体同源的16号染色体片段是三体的。成年Ts65Dn小鼠在空间任务中表现出异常学习。我们发现，该小鼠离体海马也表现出异常的长期增强（LTP）和长期抑制（LTD），这是学习和记忆的模型。然而，NMDA受体主要亚基（NR1）和α - 1c Ca2+通道亚基蛋白的表达，通过Western blotting估计，没有异常。此外，通过体内1H磁共振波谱，我们证明了Ts65Dn小鼠大脑中的肌醇水平比对照小鼠高，这与我们之前证明的唐氏综合征受试者大脑中肌醇水平升高相一致。因此，异常的磷酸肌肽信号可能与唐氏综合征的智力低下有关，可以在适当的小鼠模型中进行检查。Kainate受体介导的兴奋性突触后电流发生在脊髓中，并参与伤害感觉。我们开发的新型非nmda拮抗剂作为抗疼痛药物被证明可以干扰海碱盐在大鼠脊髓中的作用。- Kainate，长时程增强，长时程抑制，海马，唐氏综合症，65Dn三体小鼠

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