scholarly journals Endocannabinoid signaling regulates the reinforcing and psychostimulant effects of ketamine in mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei Xu ◽  
Hongchun Li ◽  
Liang Wang ◽  
Jiamei Zhang ◽  
Chunqi Liu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Caudate Nucleus ◽  
Clinical Application ◽  
Critical Role ◽  
Dorsal Striatum ◽  
Monoacylglycerol Lipase ◽  
Cannabinoid Cb1 Receptor ◽  
Dendrite Structure ◽  
Neuronal Dendrite ◽  
Reinforcing Effects

AbstractThe abuse potential of ketamine limits its clinical application, but the precise mechanism remains largely unclear. Here we discovered that ketamine significantly remodels the endocannabinoid-related lipidome and activates 2-arachidonoylglycerol (2-AG) signaling in the dorsal striatum (caudate nucleus and putamen, CPu) of mice. Elevated 2-AG in the CPu is essential for the psychostimulant and reinforcing effects of ketamine, whereas blockade of the cannabinoid CB1 receptor, a predominant 2-AG receptor, attenuates ketamine-induced remodeling of neuronal dendrite structure and neurobehaviors. Ketamine represses the transcription of the monoacylglycerol lipase (MAGL) gene by promoting the expression of PRDM5, a negative transcription factor of the MAGL gene, leading to increased 2-AG production. Genetic overexpression of MAGL or silencing of PRDM5 expression in the CPu robustly reduces 2-AG production and ketamine effects. Collectively, endocannabinoid signaling plays a critical role in mediating the psychostimulant and reinforcing properties of ketamine.

scholarly journals Striatal and hippocampal contributions to flexible navigation in rats and humans

2020 ◽  
Vol 4 ◽  
pp. 239821282097977
Author(s):  
Christoffer J. Gahnstrom ◽  
Hugo J. Spiers
Keyword(s):  
Caudate Nucleus ◽  
Spatial Navigation ◽  
Dorsal Striatum ◽  
Future Research ◽  
Neural Responses ◽  
Learning Models ◽  
Transition Structure ◽  
Cortical Areas ◽  
Reinforcement Learning Models ◽  
Human Neuroimaging

The hippocampus has been firmly established as playing a crucial role in flexible navigation. Recent evidence suggests that dorsal striatum may also play an important role in such goal-directed behaviour in both rodents and humans. Across recent studies, activity in the caudate nucleus has been linked to forward planning and adaptation to changes in the environment. In particular, several human neuroimaging studies have found the caudate nucleus tracks information traditionally associated with that by the hippocampus. In this brief review, we examine this evidence and argue the dorsal striatum encodes the transition structure of the environment during flexible, goal-directed behaviour. We highlight that future research should explore the following: (1) Investigate neural responses during spatial navigation via a biophysically plausible framework explained by reinforcement learning models and (2) Observe the interaction between cortical areas and both the dorsal striatum and hippocampus during flexible navigation.

scholarly journals Critical Role and Regulation of Transcription Factor FoxM1 in Human Gastric Cancer Angiogenesis and Progression

2009 ◽  
Vol 69 (8) ◽  
pp. 3501-3509 ◽  
Author(s):  
Qiang Li ◽  
Nu Zhang ◽  
Zhiliang Jia ◽  
Xiangdong Le ◽  
Bingbing Dai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Critical Role ◽  
Regulation Of Transcription ◽  
Human Gastric Cancer

scholarly journals Signal Transducer and Activator of Transcription (Stat) 5b-Mediated Inhibition of Insulin-Like Growth Factor Binding Protein-1 Gene Transcription: A Mechanism for Repression of Gene Expression by Growth Hormone

2007 ◽  
Vol 21 (6) ◽  
pp. 1443-1457 ◽  
Author(s):  
Mitsuru Ono ◽  
Dennis J. Chia ◽  
Roxana Merino-Martinez ◽  
Amilcar Flores-Morales ◽  
Terry G. Unterman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Transcription ◽  
Binding Protein ◽  
Critical Role ◽  
Somatic Growth ◽  
Transcript Profiling ◽  
Signal Transducer ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract GH plays a central role in controlling somatic growth, tissue regeneration, and intermediary metabolism in most vertebrate species through mechanisms dependent on the regulation of gene expression. Recent studies using transcript profiling have identified large cohorts of genes whose expression is induced by GH. Other results have demonstrated that signal transducer and activator of transcription (Stat) 5b, a latent transcription factor activated by the GH receptor-associated protein kinase, Jak2, is a key agent in the GH-stimulated gene activation that leads to somatic growth. By contrast, little is known about the steps through which GH-initiated signaling pathways reduce gene expression. Here we show that Stat5b plays a critical role in the GH-regulated inhibition of IGF binding protein-1 gene transcription by impairing the actions of the FoxO1 transcription factor on the IGF binding protein-1 promoter. Additional observations using transcript profiling in the liver indicate that Stat5b may be a general mediator of GH-initiated gene repression. Our results provide a model for understanding how GH may simultaneously stimulate and inhibit the expression of different cohorts of genes via the same transcription factor, potentially explaining how GH action leads to integrated biological responses in the whole organism.

scholarly journals The THO/TREX Complex Component RAE2/TEX1 Is Involved in the Regulation of Aluminum Resistance and Low Phosphate Response in Arabidopsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Fang Zhu ◽  
Jinliang Guo ◽  
Yang Zhang ◽  
Chao-Feng Huang
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Mrna Export ◽  
Critical Role ◽  
Core Component ◽  
Mrna Accumulation ◽  
Zinc Finger Transcription Factor ◽  
Phosphate Response ◽  
Encoding Gene ◽  
Malate Transporter

The C2H2-type zinc finger transcription factor SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) plays a critical role in aluminum (Al) resistance and low phosphate (Pi) response mainly through promoting the expression of the malate transporter-encoding gene ARABIDOPSIS THALIANA ALUMINUM ACTIVATED MALATE TRANSPORTER 1 (AtALMT1). We previously showed that REGULATION OF ATALMT1 EXPRESSION 3 (RAE3/HPR1), a core component of the THO/TREX complex, is involved in the regulation of nucleocytoplasmic STOP1 mRNA export to modulate Al resistance and low Pi response. Here, we report that RAE2/TEX1, another core component of the THO complex, is also involved in the regulation of Al resistance and low Pi response. Mutation of RAE2 reduced the expression of STOP1-downstream genes, including AtALMT1. rae2 was less sensitive to Al than rae3, which was consistent with less amount of malate secreted from rae3 roots than from rae2 roots. Nevertheless, low Pi response was impaired more in rae2 than in rae3, suggesting that RAE2 also regulates AtALMT1-independent pathway to modulate low Pi response. Furthermore, unlike RAE3 that regulates STOP1 mRNA export, mutating RAE2 did not affect STOP1 mRNA accumulation in the nucleus, although STOP1 protein level was reduced in rae2. Introduction of rae1 mutation into rae2 mutant background could partially recover the deficient phenotypes of rae2. Together, our results demonstrate that RAE2 and RAE3 play overlapping but distinct roles in the modulation of Al resistance and low Pi response.

scholarly journals The Halophyte Halostachys caspica AP2/ERF Transcription Factor HcTOE3 Positively Regulates Freezing Tolerance in Arabidopsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangliu Yin ◽  
Youling Zeng ◽  
Jieyun Ji ◽  
Pengju Wang ◽  
Yufang Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Abscisic Acid ◽  
Freezing Tolerance ◽  
Critical Role ◽  
Extreme Temperature ◽  
Freezing Stress ◽  
Antioxidant Enzyme Activities ◽  
Transcription Factor Gene ◽  
Factor Gene ◽  
Halostachys Caspica

The APETALA2 (AP2) and ethylene-responsive element-binding factor (ERF) gene family is one of the largest plant-specific transcription factor gene families, which plays a critical role in plant development and evolution, as well as response to various stresses. The TARGET OF EAT3 (TOE3) gene is derived from Halostachys caspica and belongs to the AP2 subfamily with two AP2 DNA-binding domains. Currently, AP2 family mainly plays crucial roles in plant growth and evolution, yet there are few reports about the role of AP2 in abiotic stress tolerance. Here, we report HcTOE3, a new cold-regulated transcription factor gene, which has an important contribution to freezing tolerance. The main results showed that the expression of HcTOE3 in the H. caspica assimilating branches was strongly induced by different abiotic stresses, including high salinity, drought, and extreme temperature (heat, chilling, and freezing), as well as abscisic acid and methyl viologen treatments. Overexpressing HcTOE3 gene (OE) induced transgenic Arabidopsis plant tolerance to freezing stress. Under freezing treatment, the OE lines showed lower content of malondialdehyde and electrolyte leakage and less accumulation of reactive oxygen species compared with the wild type. However, the survival rates, antioxidant enzyme activities, and contents of osmotic adjustment substance proline were enhanced in transgenic plants. Additionally, the OE lines increased freezing tolerance by up-regulating the transcription level of cold responsive genes (CBF1, CBF2, COR15, COR47, KIN1, and RD29A) and abscisic acid signal transduction pathway genes (ABI1, ABI2, ABI5, and RAB18). Our results suggested that HcTOE3 positively regulated freezing stress and has a great potential as a candidate gene to improve plant freezing tolerance.

A critical role of Sp1 transcription factor in regulating gene expression in response to insulin and other hormones

Life Sciences ◽  
2008 ◽  
Vol 83 (9-10) ◽  
pp. 305-312 ◽  
Author(s):  
Solomon S. Solomon ◽  
Gipsy Majumdar ◽  
Antonio Martinez-Hernandez ◽  
Rajendra Raghow
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Critical Role ◽  
Sp1 Transcription Factor

scholarly journals The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Yong Tang ◽  
Marie J. Desierto ◽  
Jichun Chen ◽  
Neal S. Young
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Transcription Factor ◽  
Transforming Growth Factor ◽  
Bone Marrow Failure ◽  
Critical Role ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Immune Mediated

Abstract The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet−/−). In comparison with normal C57BL6 (B6) control mice, T-bet−/− mice had normal cellular composition in lymphohematopoietic tissues, but T-bet−/− lymphocytes were functionally defective. Infusion of 5 × 106 T-bet−/− lymph node (LN) cells into sublethally irradiated, major histocompatibility complex–mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet−/− LN-cell dose to 10 to 23 × 106 per recipient led to only mild hematopoietic deficiency. Recipients of T-bet−/− LN cells had no expansion in T cells or interferon-γ–producing T cells but showed a significant increase in Lin−Sca1+CD117+CD34− BM cells. Plasma transforming growth factor-β and interleukin-17 concentrations were increased in T-bet−/− LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-γ resulted in hematopoietic suppression but did not cause T-bet−/− LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

scholarly journals The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sébastien Lyonnais ◽  
Aleix Tarrés-Solé ◽  
Anna Rubio-Cosials ◽  
Anna Cuppari ◽  
Reicy Brito ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Protein ◽  
Critical Role ◽  
Replication Initiation ◽  
Mitochondrial Transcription ◽  
Hmg Box ◽  
Conserved Sequence ◽  
Mitochondrial Transcription Factor ◽  
G Quadruplex ◽  
Mitochondrial Transcription Factor A

Abstract The ability of the guanine-rich strand of the human mitochondrial DNA (mtDNA) to form G-quadruplex structures (G4s) has been recently highlighted, suggesting potential functions in mtDNA replication initiation and mtDNA stability. G4 structures in mtDNA raise the question of their recognition by factors associated with the mitochondrial nucleoid. The mitochondrial transcription factor A (TFAM), a high-mobility group (HMG)-box protein, is the major binding protein of human mtDNA and plays a critical role in its expression and maintenance. HMG-box proteins are pleiotropic sensors of DNA structural alterations. Thus, we investigated and uncovered a surprising ability of TFAM to bind to DNA or RNA G4 with great versatility, showing an affinity similar than to double-stranded DNA. The recognition of G4s by endogenous TFAM was detected in mitochondrial extracts by pull-down experiments using a G4-DNA from the mtDNA conserved sequence block II (CSBII). Biochemical characterization shows that TFAM binding to G4 depends on both the G-quartets core and flanking single-stranded overhangs. Additionally, it shows a structure-specific binding mode that differs from B-DNA, including G4-dependent TFAM multimerization. These TFAM-G4 interactions suggest functional recognition of G4s in the mitochondria.

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