Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
Mol Cell Neurosci. 2022 May;120:103724. doi: 10.1016/j.mcn.2022.103724. Epub 2022 Mar 31.
We recently generated a novel Angelman syndrome (AS) rat model with a complete Ube3a gene deletion, that recapitulates the loss of UBE3A protein and shows cognitive and EEG deficits. We also recently published the identification of extracellular UBE3A protein within the brain using microdialysis. Here we explored the effects of supplementation of exogenous UBE3A protein to hippocampal slices and intrahippocampal injection of AS rats. We report that the AS rat model demonstrates deficits in hippocampal long-term potentiation (LTP) which can be recovered with the application of exogenous UBE3A protein. Furthermore, injection of recombinant UBE3A protein into the hippocampus of the AS rat can rescue the associative learning and memory deficits seen in the fear conditioning task. These data suggest that extracellular UBE3A protein may play a role in synaptic function, LTP induction and hippocampal-dependent memory formation.
我们最近生成了一种新型的 Angelman 综合征（AS）大鼠模型，该模型完全缺失了 Ube3a 基因，重现了 UBE3A 蛋白的缺失，并表现出认知和脑电图缺陷。我们最近还发表了使用微透析技术在大脑中鉴定细胞外 UBE3A 蛋白的方法。在这里，我们探讨了外源性 UBE3A 蛋白对海马切片的补充和 AS 大鼠海马内注射的影响。我们报告说，AS 大鼠模型表现出海马长时程增强（LTP）缺陷，而外源性 UBE3A 蛋白的应用可以恢复这种缺陷。此外，将重组 UBE3A 蛋白注射到 AS 大鼠的海马中，可以挽救在恐惧条件反射任务中观察到的联想学习和记忆缺陷。这些数据表明，细胞外 UBE3A 蛋白可能在突触功能、LTP 诱导和海马依赖性记忆形成中发挥作用。
