Bursa Uludag University School of Medicine, Department of Physiology, Bursa, Turkey.
Bursa Uludag University School of Medicine, Department of Physiology, Bursa, Turkey.
Brain Res. 2022 Oct 15;1793:148039. doi: 10.1016/j.brainres.2022.148039. Epub 2022 Aug 3.
Rapid eye movement (REM) sleep is associated with synaptic plasticity which is considered essential for long-term potentiation (LTP). The composition of extracellular matrix (ECM), in part, plays a role in REM sleep-associated synaptic functioning. The objective of this study was to investigate the effects of uridine administration on levels of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in rats subjected to REM sleep deprivation (REMSD). REMSD was induced by modified multiple platform method for 96-hour. Rats were randomized to receive either saline or uridine (1 mmol/kg) intraperitoneally twice a day for four days. Rats were then decapitated and their hippocampi were dissected for analyzing the levels of MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2 and TIMP-3 by Western-blotting and the activities of MMP-2 and MMP-9 by Gelatin zymography. REMSD resulted in reduced levels of MMP-3, MMP-9, TIMP-3 and activity of MMP-9 in saline-treated rats, while uridine treatment significantly enhanced their impairment. TIMP-1 was enhanced following REMSD but uridine treatment had no significant effect on TIMP-1 levels. MMP-2, TIMP-2 levels and MMP-2 activity were not affected by either REMSD or uridine administration. These data show that REMSD significantly affects ECM composition which is ameliorated by uridine administration suggesting a possible use of uridine in sleep disorders.
快速眼动（REM）睡眠与突触可塑性有关，而突触可塑性被认为是长时程增强（LTP）所必需的。细胞外基质（ECM）的组成部分在 REM 睡眠相关的突触功能中起作用。本研究的目的是研究尿苷给药对 REM 睡眠剥夺（REMSD）大鼠基质金属蛋白酶（MMPs）及其内源性抑制剂（TIMPs）水平的影响。采用改良的多平台法诱导 REMSD 96 小时。大鼠随机接受腹腔内生理盐水或尿苷（1mmol/kg），每天两次，连续 4 天。然后断头取脑，分离海马，用 Western-blotting 分析 MMP-2、MMP-3、MMP-9、TIMP-1、TIMP-2 和 TIMP-3 的水平，用明胶酶谱法分析 MMP-2 和 MMP-9 的活性。REMSD 导致盐水处理的大鼠中 MMP-3、MMP-9、TIMP-3 水平降低和 MMP-9 活性降低，而尿苷治疗显著增强了这种损伤。REMSD 后 TIMP-1 升高，但尿苷治疗对 TIMP-1 水平没有显著影响。MMP-2、TIMP-2 水平和 MMP-2 活性不受 REMSD 或尿苷给药的影响。这些数据表明，REMSD 显著影响 ECM 组成，而尿苷给药可改善 ECM 组成，提示尿苷在睡眠障碍中的可能应用。
