Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Department of Biological Sciences, KAIST, Daejeon, Korea.
Nat Neurosci. 2015 Mar;18(3):435-43. doi: 10.1038/nn.3927. Epub 2015 Jan 26.
Social deficits are observed in diverse psychiatric disorders, including autism spectrum disorders and schizophrenia. We found that mice lacking the excitatory synaptic signaling scaffold IRSp53 (also known as BAIAP2) showed impaired social interaction and communication. Treatment of IRSp53(-/-) mice, which display enhanced NMDA receptor (NMDAR) function in the hippocampus, with memantine, an NMDAR antagonist, or MPEP, a metabotropic glutamate receptor 5 antagonist that indirectly inhibits NMDAR function, normalized social interaction. This social rescue was accompanied by normalization of NMDAR function and plasticity in the hippocampus and neuronal firing in the medial prefrontal cortex. These results, together with the reduced NMDAR function implicated in social impairments, suggest that deviation of NMDAR function in either direction leads to social deficits and that correcting the deviation has beneficial effects.
在包括自闭症谱系障碍和精神分裂症在内的多种精神疾病中都观察到社会缺陷。我们发现，缺乏兴奋性突触信号支架 IRSp53（也称为 BAIAP2）的小鼠表现出社交互动和交流受损。用 NMDA 受体（NMDAR）拮抗剂美金刚或代谢型谷氨酸受体 5 拮抗剂 MPEP 治疗 IRSp53(-/-) 小鼠，可改善其海马中增强的 NMDAR 功能，正常化社交互动。这种社交恢复伴随着海马中 NMDAR 功能和可塑性以及内侧前额叶皮层神经元放电的正常化。这些结果，以及与社交障碍相关的 NMDAR 功能降低一起表明，NMDAR 功能的任何方向的偏差都会导致社交缺陷，而纠正这种偏差会产生有益的效果。
