ABSTRACT
Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the hippocampal lipidome in a rat model of chronic unpredictable stress(CUS).Methods:Twenty-four SD rats were randomly assigned to the following 3 groups ( n=8 for each group): sham group, CUS group and CUS+ rTMS group. The sham group received only sham stimulation and rats in the CUS and CUS+ rTMS group were subjected to CUS stimulation. Then, rats received 5 Hz rTMS (5 Hz, 1.26 Tesla) or sham rTMS for 7 days. After the last stimulation, all rats underwent sucrose preference test, open filed test and forced swimming test so as to observe the effect of rTMS on depressive behavior. Then, rats were sacrificed, and the levels of lipid composition in hippocampus were determined by high performance liquid chromatography mass spectrometry and analyzed by lipid search software version 4.1 and SIMCA-P 14.1.The software of SPSS 19.0 was used for statistical analysis. Univariate analysis of variance was used for comparison among groups, and Tukey test was used for multiple comparison. Results:(1)There were significant differences in open field test, sugar preference test and forced swimming test among the three groups( F=6.853-7.466, all P<0.05). In the open field experiment, the exploring time and percentage of movement distance in central area of rats in CUS group((50.72±6.38)s, (11.41±1.55)%) was significantly less than that of sham group ((86.06±7.31)s, (18.60±1.21)%) and CUS+ rTMS group((79.87±7.87)s, (16.74±1.27)%)(all P<0.05). The results of sucrose preference test showed that the percentage of sucrose intake of rats in CUS group ((37.63±6.06)%) was significantly lower than that in sham group ((68.30±6.39)%) and CUS+ rTMS group ((62.68±5.50)%)(both P<0.05) . In forced swimming test, the immobility time of rats in CUS group ((137.60±13.36)s) was significantly longer than that of sham group ((80.57±10.36)s)) and CUS+ rTMS group ((86.14±11.49)s) (both P<0.05). (2)The levels of lipid composition in hippocampus were significantly different in the three groups( F=3.826-15.440, all P<0.05). The contents of phosphatidylethanolamine (PE) ((20 850±956.56)×10 7, (24 133.33±1 242.04)×10 7), phosphatidylinositol (PI) ((788.78±136.11)×10 7, (953.65±131.26)×10 7), lysophosphatidylcholine (LPC) ((340.29±35.66)×10 7, (275.32±35.78)×10 7), creatine phosphate (CerP) ((239.65±18.14)×10 7, (293.82±38.28)×10 7), sphingosine (So) ((22.96±4.04)×10 7, (15.36±3.87)×10 7), diglyceride (DG) ((3.35±0.85)×10 7, (4.57±1.02)×10 7) and monoglyceride (MG) ((6.71±0.82)×10 7, (7.94±0.91)×10 7)in hippocampus of rats in CUS group were significantly higher than those of sham group(all P<0.05), while the phosphatidic acid(PA) ((424.52±33.38)×10 7, (509.22±42.09)×10 7) and acyl carnitine(AcCa) ((2.68±0.33)×10 7, (3.39±0.33)×10 7) decreased(both P<0.05). Compared with CUS group, the contents of PE(21 816.67±928.26)×10 7, PI(83.16±91.52)×10 7, LPC(323.59±33.91)×10 7, CerP(236.39±32.02)×10 7, So(23.35±4.46)×10 7, DG(3.16±0.85)×10 7 and MG(7.03±0.26)×10 7 in the hippocampus of CuS+ rTMS group decreased, while the contents of PA(421.55±44.28)×10 7 and ACCA(2.56±0.32)×10 7 in the hippocampus of CUS+ rTMS group increased (all P<0.05). Conclusion:The levels of glycerophospholipids, glyceroglycerides, sphingolipids, fatty acids and other lipids in the hippocampus of CUS model rats are abnormal. And the 5 Hz rTMS intervention can ameliorate the depression like behavior and the disturbances of lipid in hippocampus of CUS model rats.
ABSTRACT
Objective:To investigate the effects of fluoxetine (Flx) on lipidomics of hippocampal tissue in chronic unpredictable stress (CUS) model rats.Methods:A total of 30 Sprague-Dawley rats were randomly divided into Sham group, CUS group and CUS+ Flx group, with 10 rats in each group. Rats in the CUS group and CUS+ Flx group were received one or two random stimuli every day for 28 days, and then they were received intraperitoneal injection of normal saline(1 ml/kg) and fluoxetine(10 mg/kg) respectively once a day for 14 days. Rats in the Sham group were maintained in their home cages for 28 days, and then received intraperitoneal injection of saline (1 ml/kg) once a day for 14 days. The sugar water preference experiment was carried out 24 hours after the last injection, and then the rats were killed to separate the rat hippocampus. The levels of lipid composition in hippocampus were detected by high performance liquid chromatography-mass spectrometry. The relative content of lipid was analyzed by Simca-p 14.1 and LipidSearch software version 4.1. SPSS 19.0 was used for statistical analysis. One-way ANOVA or Kruskal-Wallis test was used for comparison among groups, and Bonferroni test was used for post-hoc test. Pearson correlation or Spearman correlation was used to analyze the correlation between behavioral indexes and lipid molecular level in hippocampus.Results:There was significant difference in sugar preference test among the three groups ( F=12.830, P<0.001). The percentage of sucrose intake of rats in CUS group ((43.57±12.38)%) was significantly lower than those in Sham group ((67.09±11.81)%) and CUS+ Flx group ((62.74±8.58)%) (both P<0.05). Ninety five differential lipid molecules were screened among the three groups by lipidomic analysis, mainly distributed in glycerophospholipids and sphingolipids. Among them, levels of PE (34∶1e)+ H( r=-0.477), PE(18∶1p/20∶1)+ H( r=-0.433), PE(18∶1/18∶1)+ Na( r=-0.603), PE(36∶2p)-H( r=-0.382), PE(16∶0/20∶4)-H( r=-0.464), PE(18∶0/18.2)-H( r=-0.482), PE(16∶0e/22∶6)-H( r=-0.514), PE(18∶1/20∶4)-H( r=-0.511) and CerG1 (d18∶2/24∶0+ O)+ H( r=-0.490) were negatively correlated with sucrose preference rate (all P<0.05), whereas levels of PE (42∶6p)+ Na( r=0.379), PE(34∶0p)-H( r=0.397) and SM (d22∶1/16.0)+ HCOO( r=0.388) were positively correlated with sucrose preference rate (all P<0.05). Conclusion:Flx improves the depressive-like behavior of CUS model rats, which may be related to the regulation of hippocampal glycerophospholipid and sphingolipid metabolism.
ABSTRACT
Non-coding RNAs have been classified by the length of nucleotides in short, medium and long non-coding RNAs.Typically, long non-coding RNA and microRNA regulate the development of the kidney via Six2, Hnf-1β, Bim or mTOR signaling pathways, etc.Aberrant regulation, however, will lead to congenital anomalies of the kidney and urinary tract(CAKUT). Furthermore, the environment could affect the expression activity of non-coding RNAs at the same time.This article reviews the precise role of non-coding RNAs in the development of kidney and during the formation of CAKUT, besides, the specific regulation mechanisms are explained.