scholarly journals Retrosplenial cortex in spatial memory: focus on immediate early genes mapping

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Edyta Balcerek ◽  
Urszula Włodkowska ◽  
Rafał Czajkowski
Keyword(s):  
Spatial Memory ◽  
Parietal Lobe ◽  
Hippocampal Formation ◽  
Expression Patterns ◽  
Mrna Translation ◽  
Immediate Early Genes ◽  
Retrosplenial Cortex ◽  
Immediate Early ◽  
Early Genes

AbstractThe ability to form, retrieve and update autobiographical memories is one of the most fascinating features of human behavior. Spatial memory, the ability to remember the layout of the external environment and to navigate within its boundaries, is closely related to the autobiographical memory domain. It is served by an overlapping brain circuit, centered around the hippocampus (HPC) where the cognitive map index is stored. Apart from the hippocampus, several cortical structures participate in this process. Their relative contribution is a subject of intense research in both humans and animal models. One of the most widely studied regions is the retrosplenial cortex (RSC), an area in the parietal lobe densely interconnected with the hippocampal formation. Several methodological approaches have been established over decades in order to investigate the cortical aspects of memory. One of the most successful techniques is based on the analysis of brain expression patterns of the immediate early genes (IEGs). The common feature of this diverse group of genes is fast upregulation of their mRNA translation upon physiologically relevant stimulus. In the central nervous system they are rapidly triggered by neuronal activity and plasticity during learning. There is a widely accepted consensus that their expression level corresponds to the engagement of individual neurons in the formation of memory trace. Imaging of the IEGs might therefore provide a picture of an emerging memory engram. In this review we present the overview of IEG mapping studies of retrosplenial cortex in rodent models. We begin with classical techniques, immunohistochemical detection of protein and fluorescent in situ hybridization of mRNA. We then proceed to advanced methods where fluorescent genetically encoded IEG reporters are chronically followed in vivo during memory formation. We end with a combination of genetic IEG labelling and optogenetic approach, where the activity of the entire engram is manipulated. We finally present a hypothesis that attempts to unify our current state of knowledge about the function of RSC.

scholarly journals The Expression Patterns of Cytochrome Oxidase and Immediate-Early Genes Show Absence of Ocular Dominance Columns in the Striate Cortex of Squirrel Monkeys Following Monocular Inactivation

2021 ◽  
Vol 15 ◽  
Author(s):  
Shuiyu Li ◽  
Songping Yao ◽  
Qiuying Zhou ◽  
Toru Takahata
Keyword(s):  
Cytochrome Oxidase ◽  
Striate Cortex ◽  
Ocular Dominance ◽  
Expression Patterns ◽  
Immediate Early Genes ◽  
Squirrel Monkeys ◽  
Immediate Early ◽  
Ocular Dominance Columns ◽  
Early Genes ◽  
Layer 4

Because at least some squirrel monkeys lack ocular dominance columns (ODCs) in the striate cortex (V1) that are detectable by cytochrome oxidase (CO) histochemistry, the functional importance of ODCs on stereoscopic 3-D vision has been questioned. However, conventional CO histochemistry or trans-synaptic tracer study has limited capacity to reveal cortical functional architecture, whereas the expression of immediate-early genes (IEGs), c-FOS and ZIF268, is more directly responsive to neuronal activity of cortical neurons to demonstrate ocular dominance (OD)-related domains in V1 following monocular inactivation. Thus, we wondered whether IEG expression would reveal ODCs in the squirrel monkey V1. In this study, we first examined CO histochemistry in V1 of five squirrel monkeys that were subjected to monocular enucleation or tetrodotoxin (TTX) treatment to address whether there is substantial cross-individual variation as reported previously. Then, we examined the IEG expression of the same V1 tissue to address whether OD-related domains are revealed. As a result, staining patterns of CO histochemistry were relatively homogeneous throughout layer 4 of V1. IEG expression was also moderate and homogeneous throughout layer 4 of V1 in all cases. On the other hand, the IEG expression was patchy in accordance with CO blobs outside layer 4, particularly in infragranular layers, although they may not directly represent OD clusters. Squirrel monkeys remain an exceptional species among anthropoid primates with regard to OD organization, and thus are potentially good subjects to study the development and function of ODCs.

Intestinal perfusion induces rapid activation of immediate-early genes in weaning rats

2001 ◽  
Vol 281 (4) ◽  
pp. R1274-R1282 ◽  
Author(s):  
Lan Jiang ◽  
Heather Lawsky ◽  
Relicardo M. Coloso ◽  
Mary A. Dudley ◽  
Ronaldo P. Ferraris
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
De Novo ◽  
Immediate Early Genes ◽  
Regulatory Elements ◽  
Intestinal Perfusion ◽  
Immediate Early ◽  
Mrna Levels ◽  
Early Genes

C- fos and c- jun are immediate-early genes (IEGs) that are rapidly expressed after a variety of stimuli. Products of these genes subsequently bind to DNA regulatory elements of target genes to modulate their transcription. In rat small intestine, IEG mRNA expression increases dramatically after refeeding following a 48-h fast. We used an in vivo intestinal perfusion model to test the hypothesis that metabolism of absorbed nutrients stimulates the expression of IEGs. Compared with those of unperfused intestines, IEG mRNA levels increased up to 11 times after intestinal perfusion for 0.3–4 h with Ringer solutions containing high (100 mM) fructose (HF), glucose (HG), or mannitol (HM). Abundance of mRNA returned to preperfusion levels after 8 h. Levels of c- fos and c- jun mRNA and proteins were modest and evenly distributed among enterocytes lining the villi of unperfused intestines. HF and HM perfusion markedly enhanced IEG mRNA expression along the entire villus axis. The perfusion-induced increase in IEG expression was inhibited by actinomycin-D. Luminal perfusion induces transient but dramatic increases in c- fos and c- jun expression in villus enterocytes. Induction does not require metabolizable or absorbable nutrients but may involve de novo gene transcription in cells along the villus.

scholarly journals BRD4 mediates NF-κB-dependent epithelial-mesenchymal transition and pulmonary fibrosis via transcriptional elongation

2016 ◽  
Vol 311 (6) ◽  
pp. L1183-L1201 ◽  
Author(s):  
Bing Tian ◽  
Yingxin Zhao ◽  
Hong Sun ◽  
Yueqing Zhang ◽  
Jun Yang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Immediate Early Genes ◽  
Immediate Early ◽  
Transcriptional Elongation ◽  
Mesenchymal Transition ◽  
Early Genes ◽  
Chronic Lung Diseases

Chronic epithelial injury triggers a TGF-β-mediated cellular transition from normal epithelium into a mesenchymal-like state that produces subepithelial fibrosis and airway remodeling. Here we examined how TGF-β induces the mesenchymal cell state and determined its mechanism. We observed that TGF-β stimulation activates an inflammatory gene program controlled by the NF-κB/RelA signaling pathway. In the mesenchymal state, NF-κB-dependent immediate-early genes accumulate euchromatin marks and processive RNA polymerase. This program of immediate-early genes is activated by enhanced expression, nuclear translocation, and activating phosphorylation of the NF-κB/RelA transcription factor on Ser276, mediated by a paracrine signal. Phospho-Ser276 RelA binds to the BRD4/CDK9 transcriptional elongation complex, activating the paused RNA Pol II by phosphorylation on Ser2 in its carboxy-terminal domain. RelA-initiated transcriptional elongation is required for expression of the core epithelial-mesenchymal transition transcriptional regulators SNAI1, TWIST1, and ZEB1 and mesenchymal genes. Finally, we observed that pharmacological inhibition of BRD4 can attenuate experimental lung fibrosis induced by repetitive TGF-β challenge in a mouse model. These data provide a detailed mechanism for how activated NF-κB and BRD4 control epithelial-mesenchymal transition initiation and transcriptional elongation in model airway epithelial cells in vitro and in a murine pulmonary fibrosis model in vivo. Our data validate BRD4 as an in vivo target for the treatment of pulmonary fibrosis associated with inflammation-coupled remodeling in chronic lung diseases.

scholarly journals Comparative Messenger Ribonucleic Acid Analysis of Immediate Early Genes and Sex Steroid Receptors in Human Leiomyoma and Healthy Myometrium

1997 ◽  
Vol 82 (8) ◽  
pp. 2596-2600 ◽  
Author(s):  
Monika Lessl ◽  
Michael Klotzbuecher ◽  
Silvia Schoen ◽  
Angela Reles ◽  
Klaus Stöckemann ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Immediate Early Genes ◽  
Immediate Early ◽  
Human Myometrium ◽  
Tissue Samples ◽  
Transcript Levels ◽  
Messenger Ribonucleic Acid ◽  
Early Genes

To shed light on the molecular mechanisms involved in the pathogenesis of uterine leiomyomas, transcript levels of the immediate early genes c-fos, c-myc, and c-jun and of the estrogen receptor (ER) and progesterone receptor (PR) were determined in tissue samples of human myometrium and leiomyoma. The messenger RNA (mRNA) content was analyzed by RT-PCR. mRNAs for c-fos, c-myc, c-jun, ER, and PR were detected in all 18 samples of leiomyoma and corresponding myometrial tissue collected in this study. Interestingly, in contrast to healthy tissues, we found a distinct and significant reduction of c-fos mRNA in the tumor. These data were substantiated by the finding of lowered c-Fos protein levels in leiomyomas tissues. Moreover, transcripts of c-jun and c-myc were less abundant in most of the leiomyomas than in the myometrium. This different expression of the protooncogenes in leiomyomas and myometrium was independent of the phase of the menstrual cycle in which samples were collected. In contrast to the reduced transcript levels observed for the immediate early genes, the ER and PR mRNA contents of the leiomyomas and myometrium did not differ. These results were confirmed by immunohistochemical studies for ER and PR protein. In conclusion, our data show that the deregulated expression of protooncogenes, especially of c-fos, is linked to the pathogenesis of leiomyomas. Confirmation of a potential role of downregulated c-fos levels for the benign character of these tumors requires further investigation. Additionally, the findings suggest that sex steroids do not influence the different expression patterns of c-fos, c-myc, and c-jun in leiomyomas, as compared with myometrium.

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