Department of Neuroscience, MUSC, Charleston, SC, 29425, USA.
Psychopharmacology (Berl). 2019 Nov;236(11):3291-3300. doi: 10.1007/s00213-019-05285-1. Epub 2019 Jun 14.
It has been shown that dystrobrevin-binding protein 1 gene that encodes the protein dysbindin-1 is associated with risk for cognitive deficits, and studies have shown decreases in glutamate and correlated decreases in dysbindin-1 protein in the prefrontal cortex (PFC) and hippocampus of post-mortem tissue from schizophrenia patients. The PFC and the hippocampus have been shown to play a fundamental role in cognition, and studies in dysbindin-1 null mice have shown alterations in NMDAR located in pyramidal neurons as well as perturbation in LTP and cognitive deficits. The balance between excitatory and inhibitory transmission is crucial for normal cognitive functions; however, there is a dearth of information regarding the effects of loss of dysbindin-1 in GABAergic transmission. Using in vitro whole-cell clamp recordings, Western blots, and immunohistochemistry, we report here that dysbindin-1-deficient mice exhibit a significant decrease in the frequency of sIPSCs and in the amplitude of mIPSCs and significant decreases in PV staining and protein level. These results suggest that loss of dysbindin-1 affects GABAergic transmission at pre- and postsynaptic level and decreases parvalbumin markers.
已经表明，编码蛋白 dysbindin-1 的 dystrobrevin-binding protein 1 基因与认知缺陷的风险相关，研究表明精神分裂症患者死后前额叶皮层（PFC）和海马体中的谷氨酸减少，并且 dysbindin-1 蛋白减少。已经表明，PFC 和海马体在认知中起着至关重要的作用，并且在 dysbindin-1 缺失的小鼠中进行的研究表明，位于锥体神经元中的 NMDA 受体发生改变，并且 LTP 和认知缺陷受到干扰。兴奋和抑制性传递之间的平衡对于正常的认知功能至关重要；然而，关于 GABA 能传递中缺失 dysbindin-1 的影响的信息却很少。通过体外全细胞膜片钳记录、Western blot 和免疫组织化学，我们在这里报告说，dysbindin-1 缺失的小鼠表现出 sIPSCs 的频率和 mIPSCs 的幅度明显降低，以及 PV 染色和蛋白水平的明显降低。这些结果表明，缺失 dysbindin-1 会影响突触前和突触后的 GABA 能传递，并降低 parvalbumin 标志物。
