RESUMO
The present study was aimed to explore the correlation between θ-γ neural oscillations phase-amplitude coupling (PAC) in hippocampal CA3 area and the changes of spatial identifying and cognitive ability before and after shock avoidance training in rats. According to the results of Y-type maze shock avoidance training, the rats were divided into two groups: the fast avoidance response group and the general avoidance response group. The local field potential (LFP) of hippocampal CA3 area was recorded by wireless telemetry before and after shock avoidance training. The variation of θ oscillation (3-7 Hz) and low-γ neural oscillation (30-60 Hz) PAC in hippocampal CA3 area was analyzed by MATLAB wavelet packet extraction technique. The results showed that, compared with the general avoidance response group, the fast avoidance response group exhibited higher θ-γ neural oscillation PAC in hippocampal CA3 area before training. θ-γ oscillation PAC in hippocampal CA3 area was increased in both groups after training. It was also noticed that θ-γ neural oscillation PAC of some frequency bands in the general avoidance response group were significantly higher than those in the fast avoidance response group. The results suggest that certain intensity of training can change the spatial identifying and cognitive ability of rats, and the mechanism may involve the increase of the synchrony of θ-γ neural oscillation, i.e., the enhancement of θ-γ phase-amplitude alternating frequency coupling in hippocampal neurons.
Assuntos
Hipocampo , Ritmo Teta , Animais , Cognição , Neurônios , RatosRESUMO
Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 µg/mL) and 25-hydroxycholesterol (2 µg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 µM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.
Assuntos
Antraquinonas/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Inibidores de PCSK9 , Animais , Dieta Hiperlipídica , Células Hep G2 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Ratos Wistar , Receptores de LDL/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismoRESUMO
To investigate the molecular mechanism of aging, the combination of module analysis and DNA methylation data was used to detect dynamically controlled modules for aging. Multiple differential expression networks (DENs) were constructed based on the microarray profiles across different aging groups (<70 years, 70-80 years, and >80 years). Next, a module-based approach was utilized to extract the common candidate modules across all age groups. We used Module Connectivity Dynamic Score (MCDS) to quantify the connectivity change of the common modules among the different age groups. Functional analyses were implemented for the genes in the common modules to further identify the significant biological processes. A total of two DENs were constructed. Overall 657 informative genes were screened out. When false discovery rate (FDR) was set as 0.05, we found that 148 modules were significant. Only 1 significant 2-differential modules (DMs) (module 493) with dynamic changes was discovered. Significantly, the genes in the module 493 participated in 7 significant pathways, including pentose phosphate pathway, carbon metabolism, and citrate cycle (TCA cycle). In conclusion, pathway functions [pentose phosphate pathway, carbon metabolism, citrate cycle (TCA cycle), chromosomal instability, ateroid biosynthesis, PPAR signaling pathway, and immune response] may serve as potential therapeutic targets in aging.
RESUMO
The Late Paleozoic is considered to be an important stage in the evolution of the Central Asian Orogenic Belt (CAOB). The Bogda Mountains, a northeastern branch of the Tianshan Mountains, record the complete Paleozoic history of the Tianshan orogenic belt. The tectonic and sedimentary evolution of the west Bogda area and the timing of initial uplift of the West Bogda Mountains were investigated based on detailed sedimentological study of outcrops, including lithology, sedimentary structures, rock and isotopic compositions and paleocurrent directions. At the end of the Early Permian, the West Bogda Trough was closed and an island arc was formed. The sedimentary and subsidence center of the Middle Permian inherited that of the Early Permian. The west Bogda area became an inherited catchment area, and developed a widespread shallow, deep and then shallow lacustrine succession during the Mid-Permian. At the end of the Mid-Permian, strong intracontinental collision caused the initial uplift of the West Bogda Mountains. Sedimentological evidence further confirmed that the West Bogda Mountains was a rift basin in the Carboniferous-Early Permian, and subsequently entered the Late Paleozoic large-scale intracontinental orogeny in the region.