Interhemispheric asymmetry of c-Fos expression in glomeruli and the olfactory tubercle following repeated odor stimulation

Odor adaptation allows the olfactory system to regulate sensitivity to different stimulus intensities, which is essential for preventing saturation of the cell-transducing machinery and maintaining high sensitivity to persistent and repetitive odor stimuli. Although many studies have investigated the structure and mechanisms of the mammalian olfactory system that responds to chemical sensation, few studies have considered differences in neuronal activation that depend on the manner in which the olfactory system is exposed to odorants, or examined activity patterns of olfactory-related regions in the brain under different odor exposure conditions. To address these questions, we designed three different odor exposure conditions that mimicked diverse odor environments and analyzed c-Fos-expressing cells (c-Fos+ cells) in the odor columns of the olfactory bulb (OB). We then measured differences in the proportions of c-Fos-expressing cell types depending on the odor exposure condition. Surprisingly, under the specific odor condition in which the olfactory system was repeatedly exposed to the odorant for 1 min at 5-min intervals, one of the lateral odor columns and the ipsilateral hemisphere of the olfactory tubercle had more c-Fos+ cells than the other three odor columns and the contralateral hemisphere of the olfactory tubercle. However, this interhemispheric asymmetry of c-Fos expression was not observed in the anterior piriform cortex. To confirm whether the anterior olfactory nucleus pars externa (AONpE), which connects the left and right OB, contributes to this asymmetry, AONpE-lesioned mice were analyzed under the specific odor exposure condition. Asymmetric c-Fos expression was not observed in the OB or the olfactory tubercle. These data indicate that the c-Fos expression patterns of the olfactory-related regions in the brain are influenced by the odor exposure condition and that asymmetric c-Fos expression in these regions was observed under a specific odor exposure condition due to synaptic linkage via the AONpE. © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.1

Beneficial Effects of Highly Palatable Food on the Behavioral and Neural Adversities induced by Early Life Stress Experience in Female Rats

This study examined the effects of highly palatable food during adolescence on the psycho-emotional and neural disturbances caused by early life stress experience in female rats. Female Sprague-Dawley pups were separated from dam for 3 h daily during the first two weeks of birth (MS) or left undisturbed (NH). Half of MS females received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28. Pups were subjected to the behavioral tests during young adulthood. The plasma corticosterone response to acute stress, ΔFosB and brain-derived neurotrophic factor (BDNF) levels in the brain regions were analyzed. Total caloric intake and body weight gain during the whole experimental period did not differ among the experimental groups. Cookie access during adolescence and youth improved anxiety-/depression-like behaviors by MS experience. ΔFosB expression was decreased, but BDNF was increased in the nucleus accumbens of MS females, and ΔFosB expression was normalized and BDNF was further increased following cookie access. Corticosterone response to acute stress was blunted by MS experience and cookie access did not improve it. Results suggest that cookie access during adolescence improves the psycho-emotional disturbances of MS females, and ΔFosB and/or BDNF expression in the nucleus accumbens may play a role in its underlying neural mechanisms. © 2015 Ivyspring International Publisher.1

A pathogen-derived metabolite induces microglial activation via odorant receptors

Microglia (MG), the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen-derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We hypothesized that odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, are involved in microglial activation by pathogen-derived small metabolites. We found that MG express high levels of two mouse ORs, Olfr110 and Olfr111, which recognize a pathogenic metabolite, 2-pentylfuran, secreted by Streptococcus pneumoniae. These interactions activate MG to engage in chemotaxis, cytokine production, phagocytosis, and reactive oxygen species generation. These effects were mediated through the G(alpha s)-cyclic adenosine monophosphate-protein kinase A-extracellular signal-regulated kinase and G(beta gamma)-phospholipase C-Ca2+ pathways. Taken together, our results reveal a novel interplay between the pathogen-derived metabolite and ORs, which has major implications for our understanding of microglial activation by pathogen recognition. Database Model data are available in the PMDB database under the accession number PM0082389.N

Olfactory receptors in non-chemosensory tissues

Olfactory receptors (ORs) detect volatile chemicals that lead to the initial perception of smell in the brain. The olfactory receptor (OR) is the first protein that recognizes odorants in the olfactory signal pathway and it is present in over 1,000 genes in mice. It is also the largest member of the G protein-coupled receptors (GPCRs). Most ORs are extensively expressed in the nasal olfactory epithelium where they perform the appropriate physiological functions that fit their location. However, recent whole-genome sequencing shows that ORs have been found outside of the olfactory system, suggesting that ORs may play an important role in the ectopicexpression of non-chemosensory tissues. The ectopic expressions of ORs and their physiological functions have attracted more attention recently since MOR23 and testicular hOR17-4 have been found to be involved in skeletal muscle development, regeneration, and human sperm chemotaxis, respectively. When identifying additional expression profiles and functions of ORs in non-olfactory tissues, there are limitations posed by the small number of antibodies available for similar OR genes. This review presents the results of a research series that identifies ectopic expressions and functions of ORs in non-chemosensory tissues to provide insight into future research directions. © 2012 by the The Korean Society for Biochemistry and Molecular Biology.1

Olfactory receptors in non-chemosensory tissues

Olfactory receptors (ORs) detect volatile chemicals that lead tothe initial perception of smell in the brain. The olfactory receptor(OR) is the first protein that recognizes odorants in theolfactory signal pathway and it is present in over 1,000 genesin mice. It is also the largest member of the G protein-coupledreceptors (GPCRs). Most ORs are extensively expressed in thenasal olfactory epithelium where they perform the appropriatephysiological functions that fit their location. However, recentwhole-genome sequencing shows that ORs have been foundoutside of the olfactory system, suggesting that ORs may playan important role in the ectopic expression of non-chemosensorytissues. The ectopic expressions of ORs and their physiologicalfunctions have attracted more attention recently sinceMOR23 and testicular hOR17-4 have been found to be involvedin skeletal muscle development, regeneration, and humansperm chemotaxis, respectively. When identifying additionalexpression profiles and functions of ORs in non-olfactorytissues, there are limitations posed by the small number ofantibodies available for similar OR genes. This review presentsthe results of a research series that identifies ectopic expressionsand functions of ORs in non-chemosensory tissues toprovide insight into future research directions

Current status of PET-imaging probes of beta-amyloid plaques

Alzheimer's disease (AD) is the most common form of dementia and is characterized by progressive cognitive decline and memory loss. One of pathological hallmarks of AD is the accumulation and deposition of β-amyloid (Aβ) plaques which is a potential target for the early diagnosis of AD. Positron emission tomography (PET), a sensitive radionuclide imaging technique, has provided opportunities to detect Aβ plaques of AD. PET-imaging probes of Aβ plaques have been extensively developed during the last decade. [18F]Florbetapir, the 18F-labeled PET-imaging probe of Aβ plaques, was recently approved by US Food and Drug Administration. A number of follow-on PET-imaging probes are currently being developed in academia and pharmaceutical companies. This article will discuss the recent development of PET-imaging probes from [11C]PIB to [ 18F]Florbetapir, which are in clinic trials, and several follow-on probes in preclinical stage. © 2013 The Pharmaceutical Society of Korea.1

Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review

Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in ＞ 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma. © Korean Society for Biochemistry and Molecular Biology. All rights reserved.1

Odorant receptors in cancer

Odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, detect odorants in the nose. In addition, ORs were recently shown to be expressed in many nonolfactory tissues and cells, indicating that these receptors have physiological and pathophysiological roles beyond olfaction. Many ORs are expressed by tumor cells and tissues, suggesting that they may be associated with cancer progression or may be cancer biomarkers. This review describes OR expression in various types of cancer and the association of these receptors with various types of signaling mechanisms. In addition, the clinical relevance and significance of the levels of OR expression were evaluated. Namely, levels of OR expression in cancer were analyzed based on RNA-sequencing data reported in the Cancer Genome Atlas; OR expression patterns were visualized using t-distributed stochastic neighbor embedding (t-SNE); and the associations between patient survival and levels of OR expression were analyzed. These analyses of the relationships between patient survival and expression patterns obtained from an open mRNA database in cancer patients indicate that ORs may be cancer biomarkers and therapeutic targets. [BMB Reports 2022; 55(2): 72-80] © 2022 by the The Korean Society for Biochemistry and Molecular BiologyTRU

Control of stress signaling in stem cells: crossroads of stem cells and cancer

Tumorigenesis is a relatively rare event in the human body considering the enormous number of cells composing our body and the frequent occurrence of genetic mutations in each cell. Nevertheless, the cells that happen to meet the minimum requirements can be transformed when stressed by a variety of oncogenic stimulations, then progress to form tumors. The vigorous competition between oncogenic signaling and tumor-suppressor defense is a critical determinant of cellular fate, which can be either tumorigenic transformation or cellular senescence/apoptosis depending on “who wins the battle.” Recently, a number of cancers have been reported to originate from stem cells, whose self-renewing properties are normally reduced by innate tumor suppressors. Therefore, exploring the innate mechanism by which stem cells modulate tumor suppressors to maintain their “stemness” may provide valuable clues to characterize the distinctive oncogenic susceptibility of stem cells. This review is focused on the recent advances in the field of tumorigenesis of stem cells and on the associated molecular mechanisms. © 2016, International Society of Oncology and BioMarkers (ISOBM).1

MRPrimerW: a tool for rapid design of valid high-quality primers for multiple target qPCR experiments

Design of high-quality primers for multiple target sequences is essential for qPCR experiments, but is challenging due to the need to consider both homology tests on off-target sequences and the same stringent filtering constraints on the primers. Existing web servers for primer design have major drawbacks, including requiring the use of BLAST-like tools for homology tests, lack of support for ranking of primers, TaqMan probes and simultaneous design of primers against multiple targets. Due to the large-scale computational overhead, the few web servers supporting homology tests use heuristic approaches or perform homology tests within a limited scope. Here, we describe the MRPrimerW, which performs complete homology testing, supports batch design of primers for multi-target qPCR experiments, supports design of TaqMan probes and ranks the resulting primers to return the top-1 best primers to the user. To ensure high accuracy, we adopted the core algorithm of a previously reported MapReduce-based method, MRPrimer, but completely redesigned it to allow users to receive query results quickly in a web interface, without requiring a MapReduce cluster or a long computation. MRPrimerW provides primer design services and a complete set of 341 963 135 in silico validated primers covering 99% of human and mouse genes. Free access: http://MRPrimerW.com.