scholarly journals Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches

2016 ◽  
pp. 117-138 ◽  
Author(s):  
Robert Dantzer
Keyword(s):  
Metabolism Pathway ◽  
Kynurenine Metabolism

P–182 The mechanism of mouse embryo hatching and the impact of laser drilling the zona pellucida: an RNA sequencing study

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Liu ◽  
C Jones ◽  
K Coward
Keyword(s):  
Treatment Group ◽  
Mouse Embryo ◽  
Mouse Embryos ◽  
Z Score ◽  
Rna Seq ◽  
Metabolism Pathway ◽  
Hatching Process ◽  
The Impact

Abstract Study question What is the mechanism of embryo hatching? Will laser-assisted zona pellucida (ZP) drilling alter the embryonic transcriptome? Summary answer Hatching is an ATP-dependent process. Hatching is also associated with Rho-mediated signaling. Laser-assisted ZP drilling might cause alternation in embryo metabolism. What is known already Embryo hatching is a vital process for early embryo development and implantation. Animal data suggests that hatching is the result of multiple factors, such as mechanical pressure, protease activation, and the regulation of maternal secretions. However, little is known about the regulatory signaling mechanisms and the molecules involved. In addition, despite the extensive use of laser-assisted ZP drilling in the clinic, the safety profile of this technique at molecular level is very sparse. The impact of this technique on the embryonic transcriptome has not been studied systematically. Study design, size, duration Eighty mouse embryos were randomly divided into a laser ZP drilling group (n = 40) and an untreated group (n = 40). After treatment, embryos were cultured in vitro for two days. Then, hatching blastocyst (n = 8) and pre-hatching blastocyst (n = 8) from the untreated group, and the hatching blastocyst from the treatment group (n = 8) were processed for RNA sequencing (RNA-seq). Participants/materials, setting, methods Cryopreserved 8-cell stage mouse embryos (B6C3F1 × B6D2F1) were thawed, and a laser was used to drill the embryo ZP in the treatment group. Next, the treated and untreated embryos were individually cultured in vitro to the E4.5 blastocyst stage. The resulting blastocysts were lysed individually and used for subsequent cDNA library preparation and RNA-seq. Following data quality control and alignment, the RNA-seq data were processed for differentially expressed gene analysis and downstream functional analysis. Main results and the role of chance According to the RNA-seq data, 275 differentially expressed genes (DEGs) (230 up-regulated and 45 down-regulated, adjusted P < 0.05) were identified when comparing hatching and pre-hatching blastocysts in the control groups. Analysis suggested that the trophectoderm is the primary cell type involved in hatching, and revealed the potential molecules causing increased blastocyst hydrostatic pressure (Aqp3 and Cldn4). Functional enrichment analysis suggested that ATP metabolism and protein synthesis were activated in hatching blastocysts. DEGs were found to be significantly enriched in several gene ontology terms, particularly in terms of the organization of the cytoskeleton and actin polymerisation (P < 0.0001). Furthermore, according to QIAGEN ingenuity pathway analysis results, Rho signaling was implicated in blastocyst hatching (Actb, Arpc2, Cfl1, Myl6, Pfn1, Rnd3, Septin9, z-score=2.65, P < 0.0001). Moreover, the potential role of hormones (estrogen (z-score=2.24) and prolactin (z-score=2.4)) and growth factors (AGT (z-score=2.41) and FGF2 (z-score=2.213)) were implicated in the hatching process as indicated by the upstream regulator analysis. By comparing the transcriptome between laser-treated and untreated hatching blastocysts, 47 DEGs were identified (adjusted P < 0.05) following laser-assisted ZP drilling. These genes were enriched in metabolism-related pathways (P < 0.05), including the lipid metabolism pathway (Mvd, Mvk, Aacs, Gsk3a, Pik3c2a, Aldh9a1) and the xenobiotic metabolism pathway (Aldh18a1, Aldh9a1, Keap1, and Pik3c2a). Limitations, reasons for caution Findings in mouse embryos may not be fully representative of human embryos. Furthermore, the mechanism of hatching revealed here might only reflect the hatching process of embryos in vitro. Further studies are now necessary to confirm these findings in different conditions and species to determine their clinical significance. Wider implications of the findings: Our study profiled the mouse embryo transcriptome during in vitro hatching, identified potential key genes and mechanisms for future study. In addition, for the first time, we revealed the impact of laser-assisted ZP drilling on the transcriptome, this may help us to assess and improve the existing technique. Trial registration number Not applicable

scholarly journals Role of the Sphingosine Metabolism Pathway on Neurons Against Experimental Cerebral Ischemia in Rats

2013 ◽  
Vol 4 (5) ◽  
pp. 524-532 ◽  
Author(s):  
Yu Hasegawa ◽  
Hidenori Suzuki ◽  
Orhan Altay ◽  
William Rolland ◽  
John H. Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Metabolism Pathway ◽  
Experimental Cerebral Ischemia

scholarly journals Telomeres and Cancer

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1405
Author(s):  
Hueng-Chuen Fan ◽  
Fung-Wei Chang ◽  
Jeng-Dau Tsai ◽  
Kao-Min Lin ◽  
Chuan-Mu Chen ◽  
...  
Keyword(s):  
Telomere Length ◽  
Molecular Mechanisms ◽  
Telomere Maintenance ◽  
Cancer Development ◽  
Telomere Elongation ◽  
Metabolism Pathway ◽  
Length Regulation ◽  
Telomere Length Regulation ◽  
Genome Protection

Telomeres cap the ends of eukaryotic chromosomes and are indispensable chromatin structures for genome protection and replication. Telomere length maintenance has been attributed to several functional modulators, including telomerase, the shelterin complex, and the CST complex, synergizing with DNA replication, repair, and the RNA metabolism pathway components. As dysfunctional telomere maintenance and telomerase activation are associated with several human diseases, including cancer, the molecular mechanisms behind telomere length regulation and protection need particular emphasis. Cancer cells exhibit telomerase activation, enabling replicative immortality. Telomerase reverse transcriptase (TERT) activation is involved in cancer development through diverse activities other than mediating telomere elongation. This review describes the telomere functions, the role of functional modulators, the implications in cancer development, and the future therapeutic opportunities.

Activation of TREK-1 Potassium Channel Improved Cognitive Deficits in Alzheimer's Disease Model Mice by Modulation of Glutamate Metabolic Pathway

2021 ◽  
Author(s):  
Fang Li ◽  
Shu ning Zhou ◽  
Xin Zeng ◽  
Rui Yang ◽  
Xue Xi Wang ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Cognitive Deficits ◽  
Disease Model ◽  
Memory Deficits ◽  
Potential Therapeutic Target ◽  
Metabolism Pathway ◽  
Change Trend ◽  
Role Of It ◽  
Samp8 Mice

Abstract Alzheimerʼs disease (AD) is a progressive neurodegenerative disease characterized by cognitive dysfunction. Glutamate (Glu) metabolism pathway mediated neurotoxicity is one of main factors causing memory impairment in AD. TWIK-related potassium channel-1 (TREK-1) exerts protective effect in brain ischemia, but the role of it in AD is unknown. In this study, the SAMP8 mice were used as an AD model, the age-matched SAMR1 mice as a control, we investigated the change trend of TREK-1 channel as well as AD related molecules in brains of SAMP8 mice and showed the expression levels of TREK-1 compensatory arose before 3 months of age, then began to decline. Meanwhile the levels of Tau and Glu increased with age while Ach level decreased over age. Next, using α-Linolenic acid (ALA) as an activator of TREK-1 channel, we showed that activation of TREK-1 channel improved the learning and memory deficits of SAMP8 mice aged in 6 months. Furthermore, we explored the possible mechanisms and found that the levels of molecules were closely related to the glutamate metabolism pathway. After the activation of TREK-1 channel, the damaged neurons and astrocyte were rescued, the levels of Glu and NMDAR were down-regulated, while the level of GLT-1 was up-regulated. These findings suggested that TREK-1 played the crucial role in the pathological progression of AD and activation of TREK-1 channel improved the cognitive deficits in SAMP8 mice which is mediated by Glu metabolism pathway. The TREK-1 potassium channel may be expected to be a new potential therapeutic target for AD.

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