Intragastric administration of prednisone acetate induced impairment of hippocampal long-term potentiation
Intragastric administration of prednisone acetate induced impairment of hippocampal long-term potentiation
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DOI：
10.1016/j.brainres.2023.148270
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发表时间：
2023-02-19
期刊：
影响因子：
2.9
通讯作者：
Ding，Xinghong
中科院分区：
文献类型：
--
作者：
Wang，Yao;Xiang，Shate;Ding，Xinghong
尽管临床上广泛口服醋酸泼尼松（PA），但它仍有许多不良副作用。然而，PA是否会导致海马长期增强（LTP）损伤尚不清楚。因此，本研究采用PA （5 mg/kg·d）灌胃法建立C57BL/6小鼠海马LTP损伤模型，并与皮下注射皮质酮（CORT, 50 mg/kg·d）建立LTP损伤的方法进行比较，对该方法进行评价。首先，我们的研究结果显示，与CORT相比，PA在高频刺激（HFS）后引起的群体峰值（PS, %）下降更为显著，表明PA比CORT更成功地诱导了海马LTP的损伤。其次，PA导致的记忆性能比CORT差。第三，PA引起的齿状回颗粒细胞的损伤和损失比CORT更严重。最后，PA引起谷氨酸（Glu）、n -甲基-d-天冬氨酸受体（NMDARs）和γ -氨基丁酸（GABA）水平低于CORT。总而言之，PA （5 mg/kg·d）灌胃比CORT更成功地诱导海马LTP损伤。齿状回的神经元病变以及由此引起的Glu和NMDARs（尤其是NMDAR2A）的减少可能是LTP损伤的原因。
Prednisone acetate (PA) has many adverse side effects despite the fact that oral administration of PA is widely administrated in the clinic. However, it is unknown whether PA can cause hippocampal long-term potentiation (LTP) impairment. Therefore, in our study, PA (5 mg/kg·d) through intragastric administration (gavage) was applied to establish a model of impaired hippocampal LTP in C57BL/6 mice, and the method was evaluated by comparing with another method to establish LTP impairment through subcutaneous injection of corticosterone (CORT, 50 mg/kg·d). First, our results showed PA caused a more significant decrease in population spike (PS, %) after high-frequency stimulation (HFS) than CORT, demonstrating PA induced impairment of hippocampal LTP more successfully than CORT. Second, PA caused poorer performance of memory than CORT. Third, PA caused more serious lesions and loss of the granule cell in the dentate gyrus than CORT. Finally, PA caused lower levels of glutamic acid (Glu),N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric acid (GABA) than CORT. All in all, PA (5 mg/kg·d) through intragastric administration (gavage) induced LTP impairment in the hippocampus more successfully than CORT. The neuronal lesions in the dentate gyrus and the consequent decrease of Glu and NMDARs (especially NMDAR2A) may be the cause of LTP impairment.