School of Life Sciences, Shanghai University, Shanghai 200444, PR China.
Department of Laboratory Animal Science, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, PR China.
Neuroscience. 2023 May 21;519:120-130. doi: 10.1016/j.neuroscience.2023.01.024. Epub 2023 Feb 14.
The cytoplasmic multifunctional adaptor protein β-arrestin 2 (Arrb2) is involved in the occurrence of various nervous system diseases, such as Alzheimer's disease and Parkinson's disease. Previous laboratory studies have shown that the expression and function of the Arrb2 gene was increased in valproic acid-induced autistic mice models. However, few reports have examined the possible role of Arrb2 in the pathogenesis of autism spectrum disorder. Therefore, Arrb2-deficient (Arrb2) mice were further studied to uncover the physiological function of Arrb2 in the nervous system. In this study, we found that Arrb2 mice had normal behavioral characteristics compared with wild-type mice. The autophagy marker protein LC3B was decreased in the hippocampus of Arrb2 mice compared to wild-type mice. Western blot analysis revealed that deletion of Arrb2 caused hyperactivation of Akt-mTOR signaling in the hippocampus. In addition, abnormal mitochondrial dysfunction was observed in Arrb2 hippocampal neurons, which was characterized by a reduction in mitochondrial membrane potential and adenosine triphosphate production and an increase in reactive oxygen species levels. Therefore, this study elucidates the interaction between Arrb2 and the Akt-mTOR signaling pathway and provides insights into the role of Arrb2 in hippocampal neuron autophagy.
细胞质多功能衔接蛋白β-arrestin 2（Arrb2）参与多种神经系统疾病的发生，如阿尔茨海默病和帕金森病。先前的实验室研究表明，丙戊酸诱导的自闭症小鼠模型中 Arrb2 基因的表达和功能增加。然而，很少有报道研究 Arrb2 在自闭症谱系障碍发病机制中的可能作用。因此，进一步研究了 Arrb2 缺陷（Arrb2）小鼠，以揭示 Arrb2 在神经系统中的生理功能。在这项研究中，我们发现 Arrb2 小鼠与野生型小鼠相比具有正常的行为特征。与野生型小鼠相比，Arrb2 小鼠的海马体中的自噬标志物蛋白 LC3B 减少。Western blot 分析显示，Arrb2 的缺失导致海马体中 Akt-mTOR 信号通路的过度激活。此外，还观察到 Arrb2 海马神经元中存在异常的线粒体功能障碍，其特征为线粒体膜电位降低、三磷酸腺苷生成减少以及活性氧水平升高。因此，本研究阐明了 Arrb2 与 Akt-mTOR 信号通路之间的相互作用，并深入了解了 Arrb2 在海马体神经元自噬中的作用。
