Neuron-Targeted Caveolin-1 Improves Molecular Signaling, Plasticity, and Behavior Dependent on the Hippocampus in Adult and Aged Mice.
Neuron-Targeted Caveolin-1 Improves Molecular Signaling, Plasticity, and Behavior Dependent on the Hippocampus in Adult and Aged Mice.
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DOI：
10.1016/j.biopsych.2015.09.020
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发表时间：
2017-01-15
影响因子：
10.6
通讯作者：
Head BP
中科院分区：
文献类型：
--
作者：
Mandyam CD;Schilling JM;Cui W;Egawa J;Niesman IR;Kellerhals SE;Staples MC;Busija AR;Risbrough VB;Posadas E;Grogman GC;Chang JW;Roth DM;Patel PM;Patel HH;Head BP
体外研究表明，神经元膜/脂筏(MLRs)通过聚集促生长受体和连接神经元萌发所需的细胞骨架机械来建立细胞极性。然而，MLR及其相关蛋白对神经元衰老的影响尚不清楚。在这里，我们评估了在成年(6个月大)和老年(20个月大)小鼠的海马区，神经元靶向过表达MLR支架蛋白小窝-1(通过突触素启动子；SynCav1)对生化、形态和行为变化的影响。SynCav1基因转移后，Cav-1、MLRs的表达增加，Cav-1和原肌球蛋白相关激酶B(TrkB)受体的MLR定位不受年龄和时间的影响。Cav-1在成年小鼠中的过表达促进了海马CA1区和颗粒细胞神经元顶端树突内的树突树枝形成，这一效应也在老年小鼠中观察到，尽管程度较小，表明Cav-1保留了对海马神经元结构可塑性随年龄增长的影响。CAV-1的过表达增强了成年和老年小鼠的情景恐惧记忆，显示出改善了海马区的功能。神经元靶向的Cav-1在成年和老年海马区的过表达增强了功能上的MLRs，在细胞信号和蛋白质运输中起着相应的作用。由此导致的活体海马神经元结构变化与改善海马依赖学习和记忆有关。我们的研究结果表明，Cav-1是一种治疗涉及海马区功能受损的疾病的新策略。
Studies in vitro demonstrate that neuronal membrane/lipid rafts (MLRs) establish cell polarity by clustering pro-growth receptors and tethering cytoskeletal machinery necessary for neuronal sprouting. However, the effect of MLR and MLR-associated proteins on neuronal aging is unknown. Here we assessed the impact of neuron-targeted overexpression of a MLR scaffold protein, caveolin-1 (via a synapsin promoter; SynCav1), in the hippocampus in vivo in adult (6-months-old) and aged (20-month-old) mice on biochemical, morphologic and behavioral changes. SynCav1 resulted in increased expression of Cav-1, MLRs, and MLR-localization of Cav-1 and tropomyosin-related kinase B (TrkB) receptor independent of age and time post gene transfer. Cav-1 overexpression in adult mice enhanced dendritic arborization within the apical dendrites of hippocampal CA1 and granule cell neurons, effects that were also observed in aged mice, albeit to a lesser extent, indicating preserved impact of Cav-1 on structural plasticity of hippocampal neurons with age. Cav-1 overexpression enhanced contextual fear memory in adult and aged mice demonstrating improved hippocampal function. Neuron-targeted overexpression of Cav-1 in the adult and aged hippocampus enhances functional MLRs with corresponding roles in cell signaling and protein trafficking. The resultant structural alterations in hippocampal neurons in vivo are associated with improvements in hippocampal dependent learning and memory. Our findings suggest Cav-1 as a novel therapeutic strategy in disorders involving impaired hippocampal function.
影响因子：
4.2
作者：
Jiang, Lei;Fang, Jianwen;Moore, David S.;Gogichaeva, Natalia V.;Galeva, Nadezhda A.;Michaelis, Mary L.;Zaidi, Asma
通讯作者：
Zaidi, Asma