槲皮素通过抑制胞吞增强短时程抑制效应

目的 槲皮素是一种广泛分布于药用植物中的黄酮类化合物，传统被认为具有神经保护作用。在本研究中，我们利用位于大鼠脑干的花萼状突触的突触前神经末梢的进行膜片钳记录，研究槲皮素调控突触传递和可塑性的突触前机制。方法 利用全细胞膜片钳结合膜电容记录，在突触后记录微小兴奋性突触后电流（mEPSC），在突触前神经末梢记录钙內流和神经囊泡的释放、回收以及可立即释放库（RRP）的恢复动力学。并且利用纤维刺激在轴突给予5~200 Hz的刺激，诱发突触后EPSC，记录突触后短时程抑制（STD）。结果 100 μmol/L槲皮素不影响突触后mEPSC的振幅、频率以及AMPA受体的动力学特征。在突触前神经末梢，槲皮素不改变钙内流或囊泡的释放，但显著抑制胞吐后的网格蛋白依赖的慢速胞吞。抑制胞吞会导致突触前囊泡动员的减慢，降低RRP的补充速率，并且增强高频刺激下的短时程可塑性STD。结论 本研究为槲皮素调控中枢神经突触传递提供全新的突触前神经机制，槲皮素有助于抑制中枢神经过度兴奋，进而发挥神经保护作用。

Quercetin Enhances Short-term Depression (STD) via Inhibiting Endocytosis

Quercetin, a natural flavonol compound found in traditional Chinese medicine, fruits, vegetables, and medicinal plants, has been the subject of numerous studies due to its potential therapeutic value[1]. Accumulated studies have demonstrated that quercetin can modulate neuronal excitability via different underlying mechanisms in the centralnervous system[2-3]. However, the specific effects and mechanisms of quercetin in the central nervous system are still controversial, especially in the field of basic synaptic transmission.The calyx of Held synapse displays classic features of conventional synapse, such as the presence of calcium, sodium, and potassium ion channels in the presynaptic nerve terminals, the ability to generate action potentials, and short-term synaptic plasticity[4-5]. Li et al. (Prog Biochem Biophys, 2023, 50(6): 1391-1402. DOI: 10.16476/j. pibb. 2023.0191) investigated the presynaptic effect of quercetin using capacitance measurement techniques at the giant glutamatergic central synapse, the calyx of Held,which provides a unique feasibility to study the presynaptic kinetics of synaptic transmission. The authors showed that quercetin inhibits presynaptic vesicle endocytosis without affecting calcium influx and exocytosis. The slowdown of endocytosis further leads to inhibition of vesicle mobilization and the replenishment of the readily releasable pool (RRP). In addition, the quercetin-induced inhibition of vesicle endocytosis and RRP replenishment enhances the short-term depression (STD) during high-frequency repetitive stimulation.This study provides new insights into the quercetin-modulated presynaptic mechanisms at the synapse of the calyx of Held and suggests a protective effect that prevents excessive excitatory synaptic transmission in brain circuits. On the other hand, the specific roles of quercetin in different brain regions (e. g., cortex, hippocampus) remain to be explored in combination with the whole neural circuit. Finally, extensive basic research is required to confirm the exact treatment and the mechanism of quercetin inclinical diseases.