Objective:To evaluate the role of ryanodine receptor 2 (RyR2) in postoperative cognitive dysfunction (POCD) in aged rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), POCD group (group P) and dantrolene group (group D). A rat POCD model was prepared by closed reduction and internal fixation of left tibial fractures with sevoflurane anesthesia in P and D groups. RyR inhibitor dantrolene 2 mg/kg was injected via a tail vein at 30 min before surgery in group D. Morris water maze tests were conducted on day 1 before surgery and day 7 after surgery to evaluate the cognitive function. An open field test was conducted to detect the spontaneous motor function starting from day 7 after surgery. The rats were sacrificed after the end of Morris water maze tests and hippocampal tissues were taken for determination of the expression of RyR2 and cleaved caspase-3 (by Western blot), apoptosis rate and cytoplasmic calcium ion concentrations (by flow cytometry) and for microscopic examination of the pathological changes in hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and duration of stay in the center in the open field test among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged after surgery, the number of crossing the original platform was reduced, the expression of RyR2 and cleaved caspase-3 was up-regulated, and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were increased ( P<0.05), and the pathological changes were found in the hippocampal CA1 area in group P. Compared with group P, the escape latency was significantly shortened after surgery, the number of crossing the original platform was increased, the expression of RyR2 and cleaved caspase-3 was down-regulated, and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were decreased ( P<0.05), and the pathological changes were significantly reduced in the hippocampal CA1 area in group D. Conclusions:RyR2 activation is involved in the process of POCD in aged rats, which may be associated with increased calcium overload-induced hippocampal neuronal apoptosis.

Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.

The acyl-CoA synthetase long-chain (ACSL) belongs to an enzyme encoded by a polygenic family. ACSL, located in the endoplasmic reticulum and outer mitochondrial membrane, can catalyze fatty acids to form acyl-CoA, participating in many physiological processes, such as fatty acid metabolism and membrane modification. The ACSL family plays different roles in the fatty acid metabolism of different cells, and its dysfunction can lead to conditions such as fatty liver, arteriosclerosis, and diabetes. As a major subtype of the ACSL family in the liver, ACSL family member 1 (ACSL1) is mainly involved in the maintenance of cholesterol stability, fatty acid activation, and bile acid metabolism. It is also associated with the development of certain liver diseases such as hepatocellular carcinoma and steatosis. This paper reviews differences in physiological functions and functional characteristics of ACSL family members. It also discusses the advances in studies on the role of ACSL1 in influencing lipid metabolism, regulating cellular iron death, and the development of related diseases such as liver fibrosis, hepatocellular carcinoma, cachexia, steatosis, thyroid cancer, and breast cancer.