口服L-苏糖酸镁预防长春新碱诱导的记忆和情感障碍*

Oral Administration of Magnesium-L-Threonate Prevents Vincristine-Induced Memory and Emotional Deficits*

摘要:

目的：观察L-苏糖酸镁(magnesium-L-threonate,L-TAMS)对长春新碱(Vincristine,VCR)诱导的大鼠记忆和情感障碍的影响并探讨其机制。方法：SD大鼠随机进行如下分组：Control组、VCR组、L-TAMS+VCR组(每组5~7只)。采用新颖物体识别测试(Novel Object Recognition Test,NORT)检测大鼠记忆能力；高架十字迷宫实验(Elevated Plus-Maze Test,EPMT)检测大鼠焦虑行为；强迫游泳实验(Forced Swimming Test,FST)检测大鼠抑郁行为。使用在体电生理实验技术记录海马CA3-CA1突触后诱发场电位的幅度；Western blot检测海马内N-甲基-D-天冬氨酸受体(N-Methyl-D-Aspartate-Receptors,NMDARs)亚基NR2B表达的情况；免疫荧光检测海马CA1与前扣带回皮层(Anterior Cingulate Cortex,ACC)内小胶质细胞的表达情况。结果：与Control组比较,VCR组认知系数降低,静止不动时间延长,进入高架十字迷宫开放臂的时间和次数减少,海马CA3-CA1突触后场电位幅度降低,海马内NR2B含量显著降低,海马CA1和ACC内小胶质细胞的表达增多,腹腔注射VCR之前,提前7天直至实验结束口服L-TAMS可预防VCR所引起的上述变化。结论：L-TAMS可通过上调海马突触后膜NMDARs亚基NR2B,逆转VCR引起的CA3-CA1突触后场电位幅度显著降低,改善海马突触传递受损,同时,降低大鼠海马CA1和前扣带回皮层的小胶质细胞表达,减轻神经炎症,进一步预防VCR诱导的记忆和情感功能障碍。

Abstract:

Objective:To observe the impact of magnesium-L-threonate (L-TAMS) on vincristine (VCR)-induced memory and emotional deficits in rats and explore its mechanisms. Methods:SD rats were randomly assigned to the following groups: Control group, Vincristine group, and magnesium-L-threonate + vincristine group (5~7 rats per group). Novel Object Recognition Test (NORT) was used to assess the memory of SD rats; Elevated Plus-Maze Test (EPMT) was conducted to evaluate anxiety behaviors; Forced Swimming Test (FST) was employed to assess depressive behaviors in SD rats. The amplitude of hippocampal CA3-CA1 postsynaptic evoked field potentials was recorded using in vivo electrophysiological experimental techniques; Western blot was employed to determine the expression of N-methyl-D-aspartate receptors (NMDARs) subunit NR2B protein in the hippocampus. Immunofluorescence was used to evaluate the expression of microglial cells in the CA1 of hippocampus and anterior cingulate cortex. Results: Compared to the Control group, the VCR group exhibited a decrease in recognition index, an increase in immobility time, a reduction in the time and frequency of entering the open arms of the elevated plus-maze, a decrease in the amplitude of synaptic potentials in the CA3-CA1 region of the hippocampus, a significant reduction in the expression of NR2B in the hippocampus, and an increased expression of glial cells in the CA1 region of the hippocampus and the anterior cingulate cortex (ACC). Oral administration of L-TAMS starting 7 days prior to intraperitoneal injection of VCR until the end of the experiment prevented the aforementioned changes induced by VCR. Conclusion:L-TAMS can reverse the significant reduction in CA3-CA1 postsynaptic field potentials induced by VCR by upregulating the N-methyl-D-aspartate receptor subunit NR2B in the hippocampal postsynaptic membrane, improve impaired hippocampal synaptic transmission, and reduce the expression of microglias in CA1 of the hippocampus and anterior cingulate cortex, alleviating neuroinflammatory.this further prevents VCR-induced memory and emotional functional deficits.