Impact of Autophagy Impairment on Experience- and Diet-Related Synaptic Plasticity.
Impact of Autophagy Impairment on Experience- and Diet-Related Synaptic Plasticity.
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自噬损伤对经验及饮食相关的突触可塑性的影响
DOI：
10.3390/ijms23169228
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发表时间：
2022-08-17
影响因子：
5.6
通讯作者：
Pankratov, Yuriy
中科院分区：
文献类型：
--
作者：
Lalo, Ulyana;Nezis, Ioannis P.;Pankratov, Yuriy
关键词：
饮食和运动对大脑功能的有益影响传统上归因于自噬的增强，自噬通过降解潜在有害的细胞内结构在神经保护中发挥关键作用。自噬的分子机制也被认为可以通过与突触小泡和蛋白质的运输和内吞作用的相互作用来影响突触信号传导。尽管如此，自噬在突触可塑性调节中的作用仍然难以捉摸，特别是在哺乳动物大脑中。我们使用诱导删除 Beclin1 蛋白的转基因小鼠探讨了自噬对突触传递、稳态和急性突触可塑性的影响。我们观察到 Beclin1 缺陷小鼠的谷氨酸能突触电流下调和 GABA 能突触电流上调以及新皮质和海马的长期可塑性受损。 Beclin1 缺陷还显着降低了环境丰富、热量限制及其药理学模拟物（二甲双胍和白藜芦醇）对突触传递和可塑性的影响。综上所述，我们的数据有力地支持了自噬在调节新皮质和海马的兴奋性和抑制性突触传递以及突触可塑性中的重要性。我们的结果还强烈表明，二甲双胍和白藜芦醇对急性和稳态突触可塑性的积极调节作用，以及因此它们对脑功能的有益影响，是通过自噬的调节而发生的。
The beneficial effects of diet and exercise on brain function are traditionally attributed to the enhancement of autophagy, which plays a key role in neuroprotection via the degradation of potentially harmful intracellular structures. The molecular machinery of autophagy has also been suggested to influence synaptic signaling via interaction with trafficking and endocytosis of synaptic vesicles and proteins. Still, the role of autophagy in the regulation of synaptic plasticity remains elusive, especially in the mammalian brain. We explored the impact of autophagy on synaptic transmission and homeostatic and acute synaptic plasticity using transgenic mice with induced deletion of the Beclin1 protein. We observed down-regulation of glutamatergic and up-regulation of GABAergic synaptic currents and impairment of long-term plasticity in the neocortex and hippocampus of Beclin1-deficient mice. Beclin1 deficiency also significantly reduced the effects of environmental enrichment, caloric restriction and its pharmacological mimetics (metformin and resveratrol) on synaptic transmission and plasticity. Taken together, our data strongly support the importance of autophagy in the regulation of excitatory and inhibitory synaptic transmission and synaptic plasticity in the neocortex and hippocampus. Our results also strongly suggest that the positive modulatory actions of metformin and resveratrol in acute and homeostatic synaptic plasticity, and therefore their beneficial effects on brain function, occur via the modulation of autophagy.
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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
影响因子：
120.1
作者：
Madeo, Frank;Pietrocola, Federico;Kroemer, Guido
通讯作者：
Kroemer, Guido
星形胶质细胞是运动和热量限制模仿者的观点目标。
影响因子：
4.4
作者：
Lalo U;Pankratov Y
通讯作者：
Pankratov Y
影响因子：
9.8
作者：
Lalo U;Palygin O;Rasooli-Nejad S;Andrew J;Haydon PG;Pankratov Y
通讯作者：
Pankratov Y
影响因子：
4.6
作者：
Lalo U;Palygin O;Verkhratsky A;Grant SG;Pankratov Y
通讯作者：
Pankratov Y