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Taste receptors, originally identified in taste buds, function as the periphery receptors for taste stimuli and play an important role in food choice. Cohort studies have revealed that single nucleotide polymorphisms of taste receptors such as T1R1, T1R2, T2R38 are associated with susceptibility to oral diseases like dental caries. Recent studies have demonstrated the wide expression of taste receptors in various tissues, including intestinal epithelia, respiratory tract, and gingiva, with an emerging role of participating in the interaction between mucosa surface and microorganisms via monitoring a wide range of metabolites. On the one hand, individuals with different oral microbiomes exhibited varied taste sensitivity, suggesting a potential impact of the oral microbiota composition on taste receptor function. On the other hand, animal studies and in vitro studies have uncovered that a variety of oral cells expressing taste receptors such as gingival solitary chemosensory cells, gingival epithelial cells (GECs), and gingival fibroblasts can detect bacterial signals through bitter taste receptors to trigger host innate immune responses, thus regulating oral microbial homeostasis. This review focuses on how taste receptors, particularly bitter and sweet taste receptors, mediate the oral microbiota-host interaction as well as impact the occurrence and development of oral diseases. Further studies delineating the role of taste receptors in mediating oral microbiota-host interaction will advance our knowledge in oral ecological homeostasis establishment, providing a novel paradigm and treatment target for the better management of dental infectious diseases. [ABSTRACT FROM AUTHOR]

Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs). ipRGCs regulate subconscious non-image-forming behaviors such as circadian rhythms, pupil dilation, and light-mediated mood. Previously, we and others showed that the transcription factor Tbr2 (EOMES) is required during retinal development for the formation of ipRGCs. Tbr2 is also expressed in the adult retina leading to the hypothesis that it plays a role in adult ipRGC function. To test this, we removed Tbr2 in adult mice. We found that this results in the loss of melanopsin expression in ipRGCs but does not lead to cell death or morphological changes to their dendritic or axonal termination patterns. Additionally, we found ectopic expression of Tbr2 in conventional RGCs does not induce melanopsin expression but can increase melanopsin expression in existing ipRGCs. An interesting feature of ipRGCs is their superior survival relative to conventional RGCs after an optic nerve injury. We find that loss of Tbr2 decreases the survival rate of ipRGCs after optic nerve damage suggesting that Tbr2 plays a role in ipRGC survival after injury. Lastly, we show that the GABAergic amacrine cell marker Meis2, is expressed in the majority of Tbr2-expressing displaced amacrine cells as well as in a subset of Tbr2-expressing RGCs. These findings demonstrate that Tbr2 is necessary but not sufficient for melanopsin expression, that Tbr2 is involved in ipRGC survival after optic nerve injury, and identify a marker for Tbr2-expressing displaced amacrine cells. [ABSTRACT FROM AUTHOR]

Traumatic optic neuropathy (TON) refers to a pathological condition caused by a direct or indirect insult to the optic nerves, which often leads to a partial or permanent vision deficit due to the massive loss of retinal ganglion cells (RGCs) and their axonal fibers. Retinal microglia are immune-competent cells residing in the retina. In rodent models of optic nerve crush (ONC) injury, resident retinal microglia gradually become activated, form end-to-end alignments in the vicinity of degenerating RGC axons, and actively internalized them. Some activated microglia adopt an amoeboid morphology that engulf dying RGCs after ONC. In the injured optic nerve, the activated microglia contribute to the myelin debris clearance at the lesion site. However, phagocytic capacity of resident retinal microglia is extremely poor and therefore the clearance of cellular and myelin debris is largely ineffective. The presence of growth-inhibitory myelin debris and glial scar formed by reactive astrocytes inhibit the regeneration of RGC axons, which accounts for the poor visual function recovery in patients with TON. In this Review, we summarize the current understanding of resident retinal microglia in RGC survival and axon regeneration after ONC. Resident retinal microglia play a key role in facilitating Wallerian degeneration and the subsequent axon regeneration after ONC. However, they are also responsible for producing pro-inflammatory cytokines, chemokines, and reactive oxygen species that possess neurotoxic effects on RGCs. Intraocular inflammation triggers a massive influx of blood-borne myeloid cells which produce oncomodulin to promote RGC survival and axon regeneration. However, intraocular inflammation induces chronic neuroinflammation which exacerbates secondary tissue damages and limits visual function recovery after ONC. Activated retinal microglia is required for the proliferation of oligodendrocyte precursor cells (OPCs); however, sustained activation of retinal microglia suppress the differentiation of OPCs into mature oligodendrocytes for remyelination after injury. Collectively, controlled activation of retinal microglia and infiltrating myeloid cells facilitate axon regeneration and nerve repair. Recent advance in single-cell RNA-sequencing and identification of microglia-specific markers could improve our understanding on microglial biology and to facilitate the development of novel therapeutic strategies aiming to switch resident retinal microglia's phenotype to foster neuroprotection. [ABSTRACT FROM AUTHOR]

Accelerating cases of diabetes worldwide have given rise to higher incidences of diabetic complications. MiRNAs, a much-explored class of non-coding RNAs, play a significant role in the pathogenesis of diabetes mellitus by affecting insulin release, β-cell proliferation, and dysfunction. Besides, disrupted miRNAs contribute to various complications, diabetic retinopathy, nephropathy, and neuropathy as well as severe conditions like diabetic foot. MiRNAs regulate various processes involved in diabetic complications like angiogenesis, vascularization, inflammations, and various signaling pathways like PI3K, MAPK, SMAD, and NF-KB signaling pathways. Diabetic neuropathy is the most common diabetic complication, characterized mainly by pain and numbness, especially in the legs and feet. MiRNAs implicated in diabetic neuropathy include mir-9, mir-106a, mir-146a, mir-182, miR-23a and b, miR-34a, and miR-503. The diabetic foot is the most common diabetic neuropathy, often leading to amputations. Mir-203, miR-23c, miR-145, miR-29b and c, miR-126, miR-23a and b, miR-503, and miR-34a are associated with diabetic foot. This review has been compiled to summarize miRNA involved in initiation, progression, and miRNAs affecting various signaling pathways involved in diabetic neuropathy including the diabetic foot. Besides, potential applications of miRNAs as biomarkers and therapeutic targets in this microvascular complication will also be discussed. [ABSTRACT FROM AUTHOR]

Sour taste, the taste of acids, is one of the most enigmatic of the five basic taste qualities; its function is unclear and its receptor was until recently unknown. Sour tastes are transduced in taste buds on the tongue and palate epithelium by a subset of taste receptor cells, known as type III cells. Type III cells express a number of unique markers, which allow for their identification and manipulation. These cells respond to acid stimuli with action potentials and release neurotransmitters onto afferent nerve fibers, with cell bodies in geniculate and petrosal ganglia. Here, we review classical studies of sour taste leading up to the identification of the sour receptor as the proton channel OTOP1. [ABSTRACT FROM AUTHOR]

The fungiform papilla (FP) is a gustatory and somatosensory structure incorporating chorda tympani (CT) nerve fibers that innervate taste buds (TB) and also contain somatosensory endings for touch and temperature. Hedgehog (HH) pathway inhibition eliminates TB, but CT innervation remains in the FP. Importantly, after HH inhibition, CT neurophysiological responses to taste stimuli are eliminated, but tactile responses remain. To examine CT fibers that respond to tactile stimuli in the absence of TB, we used Phox2b-Cre; Rosa26LSL−TdTomato reporter mice to selectively label CT fibers with TdTomato. Normally CT fibers project in a compact bundle directly into TB, but after HH pathway inhibition, CT fibers reorganize and expand just under the FP epithelium where TB were. This widened expanse of CT fibers coexpresses Synapsin-1, β-tubulin, S100, and neurofilaments. Further, GAP43 expression in these fibers suggests they are actively remodeling. Interestingly, CT fibers have complex terminals within the apical FP epithelium and in perigemmal locations in the FP apex. These extragemmal fibers remain after HH pathway inhibition. To identify tactile end organs in FP, we used a K20 antibody to label Merkel cells. In control mice, K20 was expressed in TB cells and at the base of epithelial ridges outside of FP. After HH pathway inhibition, K20 + cells remained in epithelial ridges but were eliminated in the apical FP without TB. These data suggest that the complex, extragemmal nerve endings within and disbursed under the apical FP are the mechanosensitive nerve endings of the CT that remain after HH pathway inhibition. [ABSTRACT FROM AUTHOR]

Many behavioral studies and histological analyses of the sense of taste have been conducted in chickens, as it plays an important role in the ingestion of feed. In recent years, various taste receptors have been analyzed, and the functions of fatty acids, umami, and bitter taste receptors in chickens have become clear. In this review, the bitter taste sense in chickens, which is the taste quality by which animals reject poisons, is discussed among a variety of taste qualities. Chickens have taste buds in the palate, the base of the oral cavity, and the root of the tongue. Bitter taste receptors, taste receptor type 2 members 1, 2, and 7 (T2R1, T2R2, and T2R7) are expressed in these tissues. According to functional analyses of bitter taste receptors and behavioral studies, T2R1 and T2R7 are thought to be especially involved in the rejection of bitter compounds in chickens. Furthermore, the antagonists of these two functional bitter taste receptors were also identified, and it is expected that such antagonists will be useful in improving the taste quality of feed materials and poultry drugs that have a bitter taste. Bitter taste receptors are also expressed in extra-oral tissues, and it has been suggested that gastrointestinal bitter taste receptors may be involved in the secretion of gastrointestinal hormones and pathogen defense mechanisms. Thus, bitter taste receptors in chickens are suspected to play major roles in taste sensing and other physiological systems. [ABSTRACT FROM AUTHOR]

Oxytocin (OT), a nonapeptide, has a variety of functions. Despite extensive studies on OTover past decades, our understanding of its neural functions and their regulation remains incomplete. OT is mainly produced in OT neurons in the supraoptic nucleus (SON), paraventricular nucleus (PVN) and accessory nuclei between the SON and PVN. OTexerts neuromodulatory effects in the brain and spinal cord. While magnocellular OT neurons in the SON and PVN mainly innervate the pituitary and forebrain regions, and parvocellular OT neurons in the PVN innervate brainstem and spinal cord, the two sets of OT neurons have close interactions histologically and functionally. OTexpression occurs at early life to promote mental and physical development, while its subsequent decrease in expression in later life stage accompanies aging and diseases. Adaptive changes in this OT system, however, take place under different conditions and upon the maturation of OT release machinery. OT can modulate social recognition and behaviors, learning and memory, emotion, reward, and other higher brain functions. OT also regulates eating and drinking, sleep and wakefulness, nociception and analgesia, sexual behavior, parturition, lactation and other instinctive behaviors. OT regulates the autonomic nervous system, and somatic and specialized senses. Notably, OT can have different modulatory effects on the same function under different conditions. Such divergence may derive from different neural connections, OT receptor gene dimorphism and methylation, and complex interactions with other hormones. In this review, brain functions of OTand their underlying neural mechanisms as well as the perspectives of their clinical usage are presented. [ABSTRACT FROM AUTHOR]

In mammalian taste buds, Type I cells comprise half of all cells. These are termed "glial-like" based on morphologic and molecular features, but there are limited studies describing their function. We tested whether Type I cells sense chemosensory activation of adjacent chemosensory (i.e., Types II and III) taste bud cells, similar to synaptic glia. Using Gad2;;GCaMP3 mice of both sexes, we confirmed by immunostaining that, within taste buds, GCaMP expression is predominantly in Type I cells (with no Type II and ~28% Type III cells expressing weakly). In dissociated taste buds, GCaMP1 Type I cells responded to bath-applied ATP (10-100 μM) but not to 5-HT (transmitters released by Type II or III cells, respectively). Type I cells also did not respond to taste stimuli (5 μM cycloheximide, 1 mM denatonium). In lingual slice preparations also, Type I cells responded to bath-applied ATP (10-100 lM). However, when taste buds in the slice were stimulated with bitter tastants (cycloheximide, denatonium, quinine), Type I cells responded robustly. Taste-evoked responses of Type I cells in the slice preparation were significantly reduced by desensitizing purinoceptors or by purinoceptor antagonists (suramin, PPADS), and were essentially eliminated by blocking synaptic ATP release (carbenoxolone) or degrading extracellular ATP (apyrase). Thus, taste-evoked release of afferent ATP from type II chemosensory cells, in addition to exciting gustatory afferent fibers, also activates glial-like Type I taste cells. We speculate that Type I cells sense chemosensory activation and that they participate in synaptic signaling, similarly to glial cells at CNS tripartite synapses. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of chronic administration of caffeine on the anatomical characteristics of taste buds, the expression level of taste receptor protein in mice, and preference for a palatable solution. We found that following a 21-day administration of caffeine, mice showed increased behavioural responses to sweet stimuli (acesulfame-K solution). Mirroring this behavioural change, chronic caffeine treatment evidently decreased the maximal cross-sectional area and height of the longitudinal axis of fungiform taste buds, the number of taste cells per fungiform taste bud, and the expression of G protein α-gustducin, while the expression of the sweet taste receptors T1R2 and T1R3 was reversed. Our findings demonstrate that chronic administration of caffeine has an impact on taste sensitivity and changes in taste bud features, which may contribute to the alteration of taste behaviour. [ABSTRACT FROM AUTHOR]

Astrocytes are an abundant subgroup of cells in the central nervous system (CNS) that play a critical role in controlling neuronal circuits involved in emotion, learning, and memory. In clinical cases, multiple chronic brain diseases may cause psychosocial and cognitive impairment, such as depression and Alzheimer's disease (AD). For years, complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability, resulting in gradual loss of self-care ability, lower life qualities, and vast burden on human society. Interestingly, correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological disease. As a kind of multifunctional glial cell in the CNS, astrocytes maintain physiological function via supporting neuronal cells, modulating pathologic niche, and regulating energy metabolism. Mounting evidence has shown that astrocytic dysfunction is involved in the progression of depression and AD. We herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD, with an implication of potential therapeutic avenue for these diseases by targeting astrocytes. [ABSTRACT FROM AUTHOR]

Bitter taste-sensing type 2 receptors (TAS2Rs or T2Rs), belonging to the subgroup of family A G-protein coupled receptors (GPCRs), are of crucial importance in the perception of bitterness. Although in the first instance, TAS2Rs were considered to be exclusively distributed in the apical microvilli of taste bud cells, numerous studies have detected these sensory receptor proteins in several extra-oral tissues, such as in pancreatic or ovarian tissues, as well as in their corresponding malignancies. Critical points of extra-oral TAS2Rs biology, such as their structure, roles, signaling transduction pathways, extensive mutational polymorphism, and molecular evolution, have been currently broadly studied. The TAS2R cascade, for instance, has been recently considered to be a pivotal modulator of a number of (patho)physiological processes, including adipogenesis or carcinogenesis. The latest advances in taste receptor biology further raise the possibility of utilizing TAS2Rs as a therapeutic target or as an informative index to predict treatment responses in various disorders. Thus, the focus of this review is to provide an update on the expression and molecular basis of TAS2Rs functions in distinct extra-oral tissues in health and disease. We shall also discuss the therapeutic potential of novel TAS2Rs targets, which are appealing due to their ligand selectivity, expression pattern, or pharmacological profiles. [ABSTRACT FROM AUTHOR]

Molecular insights into the selective vulnerability of retinal ganglion cells (RGCs) in optic neuropathies and after ocular trauma can lead to the development of novel therapeutic strategies aimed at preserving RGCs. However, little is known about what molecular contexts determine RGC susceptibility. In this study, we show the molecular mechanisms underlying the regional differential vulnerability of RGCs after optic nerve injury. We identified RGCs in the mouse peripheral ventrotemporal (VT) retina as the earliest population of RGCs susceptible to optic nerve injury. Mechanistically, the serotonin transporter (SERT) is upregulated on VT axons after injury. Utilizing SERT-deficient mice, loss of SERT attenuated VT RGC death and led to robust retinal axon regeneration. Integrin β3, a factor mediating SERT-induced functions in other systems, is also upregulated in RGCs and axons after injury, and loss of integrin β3 led to VT RGC protection and axon regeneration. Finally, RNA sequencing analyses revealed that loss of SERT significantly altered molecular signatures in the VT retina after optic nerve injury, including expression of the transmembrane protein, Gpnmb. GPNMB is rapidly downregulated in wild-type, but not SERT- or integrin β3-deficient VT RGCs after injury, and maintaining expression of GPNMB in RGCs via AAV2 viruses even after injury promoted VT RGC survival and axon regeneration. Taken together, our findings demonstrate that the SERT-integrin β3-GPNMB molecular axis mediates selective RGC vulnerability and axon regeneration after optic nerve injury. Author summary: Retinal ganglion cells (RGCs) are the only neurons in the retina that convey visual information to the brain, doing so via the optic nerve. Major causes of optic nerve damage and subsequent RGC death are ocular trauma and optic neuropathies. At the end-stage pathology in the retina, remaining RGCs have high neuroprotective capacity, and active resilience mechanisms exist. In contrast, in this study, we demonstrate neurodegenerative mechanisms based on the early susceptibility of peripheral ventrotemporal (VT) RGCs to degeneration after optic nerve injury. We identified the serotonin transporter (SERT) as the factor mediating VT RGC vulnerability and axon regeneration. Loss of SERT affected activation of integrin β3 and gene expression in the peripheral VT retina, leading to peripheral VT RGC protection and axon regeneration. Interestingly, GPNMB, a newly identified molecule mediating neuroprotection and axon regeneration in this study, is expressed in all retinal regions. However, GPNMB expression is acutely downregulated by the presence of SERT in the peripheral VT retina, leading to regional differential vulnerability of RGCs. These findings provide new molecular mechanisms underlying selective RGC vulnerability and clues that could inform further neuroprotective and regenerative strategies. [ABSTRACT FROM AUTHOR]

Chemosensory receptors are expressed primarily in sensory organs, but their expression elsewhere can permit ligand detection in other contexts that contribute to survival. The ability of sweet taste receptors to detect natural sugars, sugar alcohols, and artificial sweeteners suggests sweet taste receptors are involved in metabolic regulation in both peripheral organs and in the central nervous system. Our limited knowledge of sweet taste receptor expression in the brain, however, has made it difficult to assess their contribution to metabolic regulation. We, therefore, decided to profile the expression pattern of T1R2, a subunit specific to the sweet taste receptor complex, at the whole-brain level. Using T1r2-Cre knock-in mice, we visualized the overall distribution of Cre -labeled cells in the brain. T1r2-Cre is expressed not only in various populations of neurons, but also in glial populations in the circumventricular organs and in vascular structures in the cortex, thalamus, and striatum. Using immunohistochemistry, we found that T1r2 is expressed in hypothalamic neurons expressing neuropeptide Y and proopiomelanocortin in arcuate nucleus. It is also co-expressed with a canonical taste signaling molecule in perivascular cells of the median eminence. Our findings indicate that sweet taste receptors have unidentified functions in the brain and suggest that they may be a novel therapeutic target in the central nervous system. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence indicates that long noncoding RNAs (lncRNAs) are important regulators of various biological processes, and their expression can be altered following certain pathological conditions, including central nervous system injury. Retinal ganglion cells (RGCs), whose axons form the optic nerve, are a heterogeneous population of neurons with more than 40 molecularly distinct subtypes in mouse. While most RGCs, including the ON-OFF direction-selective RGCs (ooDSGCs), are vulnerable to axonal injury, a small population of RGCs, including the intrinsically photosensitive RGCs (ipRGCs), are more resilient. Results: By performing systematic analyses on RNA-sequencing data, here we identify lncRNAs that are expressed in ooDSGCs and ipRGCs with and without axonal injury. Our results reveal a repertoire of different classes of lncRNAs, including long intergenic noncoding RNAs and antisense ncRNAs that are differentially expressed between these RGC types. Strikingly, we also found dozens of lncRNAs whose expressions are altered markedly in response to axonal injury, some of which are expressed exclusively in either one of the types. Moreover, analyses into these lncRNAs unraveled their neighboring coding genes, many of which encode transcription factors and signaling molecules, suggesting that these lncRNAs may act in cis to regulate important biological processes in these neurons. Lastly, guilt-by-association analysis showed that lncRNAs are correlated with apoptosis associated genes, suggesting potential roles for these lncRNAs in RGC survival. Conclusions: Overall, the results of this study reveal RGC type-specific expression of lncRNAs and provide a foundation for future investigation of the function of lncRNAs in regulating neuronal type specification and survival. [ABSTRACT FROM AUTHOR]

Lowered glucose availability, sensed by the hindbrain, has been suggested to enhance gluconeogenesis and food intake as well as suppress reproductive function. In fact, our previous histological and in vitro studies suggest that hindbrain ependymal cells function as a glucose sensor. The present study aimed to clarify the hindbrain glucose sensor-hypothalamic neural pathway activated in response to hindbrain glucoprivation to mediate counterregulatory physiological responses. Administration of 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, into the fourth ventricle (4V) of male rats for 0.5 hour induced messenger RNA (mRNA) expression of c-fos , a marker for cellular activation, in ependymal cells in the 4V, but not in the lateral ventricle, the third ventricle or the central canal without a significant change in blood glucose and testosterone levels. Administration of 2DG into the 4V for 1 hour significantly increased blood glucose levels, food intake, and decreased blood testosterone levels. Simultaneously, the expression of c-Fos protein was detected in the 4V ependymal cells; dopamine β-hydroxylase-immunoreactive cells in the C1, C2, and A6 regions; neuropeptide Y (NPY) mRNA-positive cells in the C2; corticotropin-releasing hormone (CRH) mRNA-positive cells in the hypothalamic paraventricular nucleus (PVN); and NPY mRNA-positive cells in the arcuate nucleus (ARC). Taken together, these results suggest that lowered glucose availability, sensed by 4V ependymal cells, activates hindbrain catecholaminergic and/or NPY neurons followed by CRH neurons in the PVN and NPY neurons in the ARC, thereby leading to counterregulatory responses, such as an enhancement of gluconeogenesis, increased food intake, and suppression of sex steroid secretion. [ABSTRACT FROM AUTHOR]

Taste buds are localized in fungiform (FF), foliate (FL), and circumvallate (CV) papillae on the tongue, and taste buds also occur on the soft palate (SP). Mature elongate cells within taste buds are constantly renewed from stem cells and classified into three cell types, Types I, II, and III. These cell types are generally assumed to reside in respective taste buds in a particular ratio corresponding to taste regions. A variety of cell-type markers were used to analyze taste bud cells. NCAM is the first established marker for Type III cells and is still often used. However, NCAM was examined mainly in the CV, but not sufficiently in other regions. Furthermore, our previous data suggested that NCAM may be transiently expressed in the immature stage of Type II cells. To precisely assess NCAM expression as a Type III cell marker, we first examined Type II and III cell-type markers, IP3R3 and CA4, respectively, and then compared NCAM with them using whole-mount immunohistochemistry. IP3R3 and CA4 were segregated from each other, supporting the reliability of these markers. The ratio between Type II and III cells varied widely among taste buds in the respective regions (Pearson's r = 0.442 [CV], 0.279 [SP], and − 0.011 [FF]), indicating that Type II and III cells are contained rather independently in respective taste buds. NCAM immunohistochemistry showed that a subset of taste bud cells were NCAM(+)CA4(−). While NCAM(+)CA4(−) cells were IP3R3(−) in the CV, the majority of them were IP3R3(+) in the SP and FF. [ABSTRACT FROM AUTHOR]

Bitter taste receptors (TAS2Rs) and their signaling elements are detected throughout the body, and bitter tastants induce a wide variety of biological responses in tissues and organs outside the mouth. However, the roles of TAS2Rs in these responses remain to be tested and established genetically. Here, we employed the CRISPR/Cas9 gene‐editing technique to delete three bitter taste receptors—Tas2r143/Tas2r135/Tas2r126 (i.e., Tas2r triple knockout [TKO]) in mice. The fidelity and effectiveness of the Tas2r deletions were validated genetically at DNA and messenger RNA levels and functionally based on the tasting of TAS2R135 and TAS2R126 agonists. Bitter tastants are known to relax airways completely. However, TAS2R135 or TAS2R126 agonists either failed to induce relaxation of pre‐contracted airways in wild‐type mice and Tas2r TKO mice or relaxed them dose‐dependently, but to the same extent in both types of mice. These results indicate that TAS2Rs are not required for bitter tastant‐induced bronchodilation. The Tas2r TKO mice also provide a valuable model to resolve whether TAS2Rs mediate bitter tastant‐induced responses in many other extraoral tissues. [ABSTRACT FROM AUTHOR]

Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood and there is growing evidence that genetics play a role in the susceptibility for the disease. Familial clustering has been observed and has led to several studies on familial SSNS trying to identify a monogenic cause of the disease. Until now, however, none of these have provided convincing evidence for Mendelian inheritance. This and the phenotypic variability within SSNS suggest a complex inheritance pattern, where multiple variants and interactions between those and the environment play roles in disease development. Genome-wide association studies (GWASs) have been used to investigate this complex disease. We herein highlight new insights in the genetics of the disease provided by GWAS and identify how these insights fit into our understanding of the pathogenesis of SSNS. [ABSTRACT FROM AUTHOR]

Sweetness is the preferred taste of humans and many animals, likely because sugars are a primary source of energy. In many mammals, sweet compounds are sensed in the tongue by the gustatory organ, the taste buds. Here, a group of taste bud cells expresses a canonical sweet taste receptor, whose activation induces Ca2+ rise, cell depolarization and ATP release to communicate with afferent gustatory nerves. The discovery of the sweet taste receptor, 20 years ago, was a milestone in the understanding of sweet signal transduction and is described here from a historical perspective. Our review briefly summarizes the major findings of the canonical sweet taste pathway, and then focuses on molecular details, about the related downstream signaling, that are still elusive or have been neglected. In this context, we discuss evidence supporting the existence of an alternative pathway, independent of the sweet taste receptor, to sense sugars and its proposed role in glucose homeostasis. Further, given that sweet taste receptor expression has been reported in many other organs, the physiological role of these extraoral receptors is addressed. Finally, and along these lines, we expand on the multiple direct and indirect effects of sugars on the brain. In summary, the review tries to stimulate a comprehensive understanding of how sweet compounds signal to the brain upon taste bud cells activation, and how this gustatory process is integrated with gastro-intestinal sugar sensing to create a hedonic and metabolic representation of sugars, which finally drives our behavior. Understanding of this is indeed a crucial step in developing new strategies to prevent obesity and associated diseases. [ABSTRACT FROM AUTHOR]

Neuromodulation influences neuronal processing, conferring neuronal circuits the flexibility to integrate sensory inputs with behavioral states and the ability to adapt to a continuously changing environment. In this original research report, we broadly discuss the basis of neuromodulation that is known to regulate intrinsic firing activity, synaptic communication, and voltage-dependent channels in the olfactory bulb. Because the olfactory system is positioned to integrate sensory inputs with information regarding the internal chemical and behavioral state of an animal, how olfactory information is modulated provides flexibility in coding and behavioral output. Herein we discuss how neuronal microcircuits control complex dynamics of the olfactory networks by homing in on a special class of local interneurons as an example. While receptors for neuromodulation and metabolic peptides are widely expressed in the olfactory circuitry, centrifugal serotonergic and cholinergic inputs modulate glomerular activity and are involved in odor investigation and odor-dependent learning. Little is known about how metabolic peptides and neuromodulators control specific neuronal subpopulations. There is a microcircuit between mitral cells and interneurons that is comprised of deep-short-axon cells in the granule cell layer. These local interneurons express pre-pro-glucagon (PPG) and regulate mitral cell activity, but it is unknown what initiates this type of regulation. Our study investigates the means by which PPG neurons could be recruited by classical neuromodulators and hormonal peptides. We found that two gut hormones, leptin and cholecystokinin, differentially modulate PPG neurons. Cholecystokinin reduces or increases spike frequency, suggesting a heterogeneous signaling pathway in different PPG neurons, while leptin does not affect PPG neuronal firing. Acetylcholine modulates PPG neurons by increasing the spike frequency and eliciting bursts of action potentials, while serotonin does not affect PPG neuron excitability. The mechanisms behind this diverse modulation are not known, however, these results clearly indicate a complex interplay of metabolic signaling molecules and neuromodulators that may fine-tune neuronal microcircuits. [ABSTRACT FROM AUTHOR]

Pannexin‐1 (Panx1) forms plasma membrane channels that allow the exchange of small molecules between the intracellular and extracellular compartments, and are involved in diverse physiological and pathological responses in the nervous system. However, the signaling mechanisms that induce their opening still remain elusive. Here, we propose a new mechanism for Panx1 channel activation through a functional crosstalk with the highly Ca2+ permeable α7 nicotinic acetylcholine receptor (nAChR). Consistent with this hypothesis, we found that activation of α7 nAChRs induces Panx1‐mediated dye uptake and ATP release in the neuroblastoma cell line SH‐SY5Y‐α7. Using membrane permeant Ca2+ chelators, total internal reflection fluorescence microscopy in SH‐SY5Y‐α7 cells expressing a membrane‐tethered GCAMP3, and Src kinase inhibitors, we further demonstrated that Panx1 channel opening depends on Ca2+ signals localized in submembrane areas, as well as on Src kinases. In turn, Panx1 channels amplify cytosolic Ca2+ signals induced by the activation of α7 nAChRs, by a mechanism that seems to involve ATP release and P2X7 receptor activation, as hydrolysis of extracellular ATP with apyrase or blockage of P2X7 receptors with oxidized ATP significantly reduces the α7 nAChR‐Ca2+ signal. The physiological relevance of this crosstalk was also demonstrated in neuroendocrine chromaffin cells, wherein Panx1 channels and P2X7 receptors contribute to the exocytotic release of catecholamines triggered by α7 nAChRs, as measured by amperometry. Together these findings point to a functional coupling between α7 nAChRs, Panx1 channels and P2X7 receptors with physiological relevance in neurosecretion. [ABSTRACT FROM AUTHOR]

Action potentials play an important role in neurotransmitter release in response to taste. Here, I have investigated voltage-gated Na+ channels, a primary component of action potentials, in respective cell types of mouse fungiform taste bud cells (TBCs) with in situ whole-cell clamping and single-cell RT-PCR techniques. The cell types of TBCs electrophysiologically examined were determined immunohistochemically using the type III inositol 1,4,5-triphoshate receptor as a type II cell marker and synaptosomal-associated protein 25 as a type III cell marker. I show that type II cells, type III cells, and TBCs not immunoreactive to these markers (likely type I cells) generate voltage-gated Na+ currents. The recovery following inactivation of these currents was well fitted with double exponential curves. The time constants in type III cells (~20 ms and ~ 1 s) were significantly slower than respective time constants in other cell types. RT-PCR analysis indicated the expression of Nav1.3, Nav1.5, Nav1.6, and β1 subunit mRNAs in TBCs. Pharmacological inhibition and single-cell RT-PCR studies demonstrated that type II and type III cells principally express tetrodotoxin (TTX)-sensitive Nav1.3 channels and that ~ 30% of type I cells express TTX-resistant Nav1.5 channels. The auxiliary β1 subunit that modulates gating kinetics was rarely detected in TBCs. As the β1 subunit co-expressed with an α subunit is known to accelerate the recovery from inactivation, it is likely that voltage-gated Na+ channels in TBCs may function without β subunits. Slow recovery from inactivation, especially in type III cells, may limit high-frequency firing in response to taste substances. [ABSTRACT FROM AUTHOR]

Taste sensation is the gatekeeper for direct decisions on feeding behavior and evaluating the quality of food. Nutritious and beneficial substances such as sugars and amino acids are represented by sweet and umami tastes, respectively, whereas noxious substances and toxins by bitter or sour tastes. Essential electrolytes including Na+ and other ions are recognized by the salty taste. Gustatory information is initially generated by taste buds in the oral cavity, projected into the central nervous system, and finally processed to provide input signals for food recognition, regulation of metabolism and physiology, and higher-order brain functions such as learning and memory, emotion, and reward. Therefore, understanding the peripheral taste system is fundamental for the development of technologies to regulate the endocrine system and improve whole-body metabolism. In this review article, we introduce previous widely-accepted views on the physiology and genetics of peripheral taste cells and primary gustatory neurons, and discuss key findings from the past decade that have raised novel questions or solved previously raised questions. [ABSTRACT FROM AUTHOR]

Mice of the C57BL/6ByJ (B6) strain have higher consumption of sucrose, and stronger peripheral neural responses to it, than do mice of the 129P3/J (129) strain. To identify quantitative trait loci (QTLs) responsible for this strain difference and to evaluate the contribution of peripheral taste responsiveness to individual differences in sucrose intake, we produced an intercross (F2) of 627 mice, measured their sucrose consumption in two-bottle choice tests, recorded the electrophysiological activity of the chorda tympani nerve elicited by sucrose in a subset of F2 mice, and genotyped the mice with DNA markers distributed in every mouse chromosome. We confirmed a sucrose consumption QTL (Scon2, or Sac) on mouse chromosome (Chr) 4, harboring the Tas1r3 gene, which encodes the sweet taste receptor subunit TAS1R3 and affects both behavioral and neural responses to sucrose. For sucrose consumption, we also detected five new main-effect QTLs, Scon6 (Chr2), Scon7 (Chr5), Scon8 (Chr8), Scon3 (Chr9), and Scon9 (Chr15), and an epistatically interacting QTL pair Scon4 (Chr1) and Scon3 (Chr9). No additional QTLs for the taste nerve responses to sucrose were detected besides Scon2 (Tas1r3) on Chr4. Identification of the causal genes and variants for these sucrose consumption QTLs may point to novel mechanisms beyond peripheral taste sensitivity that could be harnessed to control obesity and diabetes. [ABSTRACT FROM AUTHOR]

Transmitter signalling is the universal chemical language of any nervous system, but little is known about its early evolution. Here, we summarize data about the distribution and functions of neurotransmitter systems in basal metazoans as well as outline hypotheses of their origins. We explore the scenario that neurons arose from genetically different populations of secretory cells capable of volume chemical transmission and integration of behaviours without canonical synapses. The closest representation of this primordial organization is currently found in Placozoa, disk-like animals with the simplest known cell composition but complex behaviours. We propose that injury-related signallingwas the evolutionary predecessor for integrative functions of early transmitters such as nitric oxide, ATP, protons, glutamate and small peptides. By contrast, acetylcholine, dopamine, noradrenaline, octopamine, serotonin and histamine were recruited as canonical neurotransmitters relatively later in animal evolution, only in bilaterians. Ligand-gated ion channels often preceded the establishment of novel neurotransmitter systems. Moreover, lineage-specific diversification of neurotransmitter receptors occurred in parallel within Cnidaria and several bilaterian lineages, including acoels. In summary, ancestral diversification of secretory signal molecules provides unique chemical microenvironments for behaviour-driven innovations that pave the way to complex brain functions and elementary cognition. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'. [ABSTRACT FROM AUTHOR]

Umami, as one of the five basic tastes, is important to the taste of food. In this study, gel filtration chromatography and reversed‐phase high‐performance liquid chromatography were used to isolate and purify Leccinum extremiorientale cooked at high temperature. Sensory evaluation and taste dilution analysis were used to identify the most umami component in L. extremiorientale. Most umami components were determined by LC‐MS/MS. Three umami peptides were identified, and they were Asp‐Gln‐Glu‐Asp‐Leu‐Asp‐Glu‐Ser‐Leu‐Ile‐Gly‐Val‐Lys (DQEDLDESLIGVK), Phe‐Asn‐Glu‐Ile‐Ile‐Lys‐Glu‐Thr‐Ser‐Thr (FNEIIKETST), Tyr‐Asn‐Glu‐Tyr‐Pro‐Pro‐Leu‐Gly‐Arg (YNEYPPLGR). As far as we know, this is the first time that umami peptides have been extracted from Boletus. This study can provide a basis for the development of delicious food with Boletus characteristics. Novelty impact statement: Three umami peptides were isolated and purified from Leccinum extremiorientale for the first time. The structure characteristics of the umami peptides were analyzed according to the sequence. The results can provide practical application for the food industry. [ABSTRACT FROM AUTHOR]

The known seven mammalian receptor subunits (P2X1-7) form cationic channels gated by ATP. Three subunits compose a receptor channel. Each subunit is a polypeptide consisting of two transmembrane regions (TM1 and TM2), intracellular N- and C-termini, and a bulky extracellular loop. Crystallization allowed the identification of the 3D structure and gating cycle of P2X receptors. The agonist-binding pocket is located at the intersection of two neighbouring subunits. In addition to the mammalian P2X receptors, their primitive ligand-gated counterparts with little structural similarity have also been cloned. Selective agonists for P2X receptor subtypes are not available, but medicinal chemistry supplied a range of subtype-selective antagonists, as well as positive and negative allosteric modulators. Knockout mice and selective antagonists helped to identify pathological functions due to defective P2X receptors, such as male infertility (P2X1), hearing loss (P2X2), pain/cough (P2X3), neuropathic pain (P2X4), inflammatory bone loss (P2X5), and faulty immune reactions (P2X7). [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Loss of taste or inability to distinguish between different tastes progresses with age. The purpose was to evaluate the age‐dependent changes in taste by studying the electrophysiological properties of taste receptor cells.What is the main finding and its importance?Ageing decreased the voltage‐gated Na+ and K+ current densities of type III cells (sour and/or salt receptor cells) but did not affect the current densities in type II cells. At the peripheral levels, the excitability of type III cells was reduced due to ageing, which may affect the signal transduction to taste nerves. The loss of taste due to normal ageing in mammals is assumed to be caused by the ageing of taste receptor cells. We examined the electrophysiological properties of taste receptor cells in the fungiform taste buds of ∼20‐month‐old mice in situ and subsequently identified their cell types with immunological markers: the inositol 1,4,5‐trisphosphate (IP3) receptor (IP3R3) for type II cells and a SNARE protein, synaptosomal‐associated protein 25 (SNAP‐25), for type III cells. Other cells are referred to as non‐immunoreactive cells (non‐IRCs). Cell types of some cells that could not be identified using cell‐type markers were identified based on the electrophysiological feature of the respective cell types. All cell types generated action potentials and a variety of voltage‐gated currents. The type II cells mainly expressed tetraethylammonium (TEA)‐insensitive and slowly activating outwardly rectifying currents and generated tail currents in repolarization. In contrast, the type III cells expressed TEA‐sensitive and faster activating K+ currents and did not generate tail currents. These cell type‐specific characteristics of voltage‐gated currents in ∼20‐month‐old mice were similar to their respective cell types in ∼2‐month‐old mice. Also, we showed an age‐dependent decrease in Na+ and K+ current densities in type III cells and an age‐dependent increase in outwardly rectifying current density in non‐IRCs. Ageing did not affect the voltage‐gated current densities in type II cells. The decreased Na+ and K+ current densities, i.e. the decreased excitability of type III cells, due to ageing may affect the signal transduction to taste nerves. [ABSTRACT FROM AUTHOR]

Mammalian taste bud cells have a limited lifespan and differentiate into type I, II, and III cells from basal cells (type IV cells) (postmitotic precursor cells). However, little is known regarding the cell lineage within taste buds. In this study, we investigated the cell fate of Mash1-positive precursor cells utilizing the Cre-loxP system to explore the differentiation of taste bud cells. We found that Mash1-expressing cells in Ascl1CreERT2::CAG-floxed tdTomato mice differentiated into taste bud cells that expressed aromatic L-amino acid decarboxylase (AADC) and carbonic anhydrase IV (CA4) (type III cell markers), but did not differentiate into most of gustducin (type II cell marker)-positive cells. Additionally, we found that Mash1-expressing cells could differentiate into phospholipase C β2 (PLCβ2)-positive cells, which have a shorter lifespan compared with AADC- and CA4-positive cells. These results suggest that Mash1-positive precursor cells could differentiate into type III cells, but not into most of type II cells, in the taste buds. [ABSTRACT FROM AUTHOR]

The variety of taste sensations, including sweet, umami, bitter, sour, and salty, arises from diverse taste cells, each of which expresses specific taste sensor molecules and associated components for downstream signal transduction cascades. Recent years have witnessed major advances in our understanding of the molecular mechanisms underlying transduction of basic tastes in taste buds, including the identification of the bona fide sour sensor H+ channel OTOP1, and elucidation of transduction of the amiloride-sensitive component of salty taste (the taste of sodium) and the TAS1R-independent component of sweet taste (the taste of sugar). Studies have also discovered an unconventional chemical synapse termed "channel synapse" which employs an action potential-activated CALHM1/3 ion channel instead of exocytosis of synaptic vesicles as the conduit for neurotransmitter release that links taste cells to afferent neurons. New images of the channel synapse and determinations of the structures of CALHM channels have provided structural and functional insights into this unique synapse. In this review, we discuss the current view of taste transduction and neurotransmission with emphasis on recent advances in the field. [ABSTRACT FROM AUTHOR]

In taste buds, Type I cells represent the majority of cells (50–60%) and primarily have a glial-like function in taste buds. However, recent studies suggest that they have additional sensory and signaling functions including amiloride-sensitive salt transduction, oxytocin modulation of taste, and substance P mediated GABA release. Nonetheless, the overall function of Type I cells in transduction and signaling remains unclear, primarily because of the lack of a reliable reporter for this cell type. GAD65 expression is specific to Type I taste cells and GAD65 has been used as a Cre driver to study Type I cells in salt taste transduction. To test the specificity of transgene-driven expression, we crossed GAD65Cre mice with floxed tdTomato and Channelrhodopsin (ChR2) lines and examined the progeny with immunochemistry, chorda tympani recording, and calcium imaging. We report that while many tdTomato+ taste cells express NTPDase2, a specific marker of Type I cells, we see some expression of tdTomato in both Gustducin and SNAP25-positive taste cells. We also see ChR2 in cells just outside the fungiform taste buds. Chorda tympani recordings in the GAD65Cre/ChR2 mice show large responses to blue light. Furthermore, several isolated tdTomato-positive taste cells responded to KCl depolarization with increases in intracellular calcium, indicating the presence of voltage-gated calcium channels. Taken together, these data suggest that GAD65Cre mice drive expression in multiple taste cell types and thus cannot be considered a reliable reporter of Type I cell function. [ABSTRACT FROM AUTHOR]

The T1R and T2R families of G protein-coupled receptors (GPCRs) initiate tastant perception by signaling via guanine nucleotide exchange and hydrolysis performed by associated heterotrimeric G proteins (Gαβγ). Heterotrimeric G protein signal termination is sped up by Gα-directed GTPase-accelerating proteins (GAPs) known as the Regulators of G protein Signaling (RGS proteins). Of this family, RGS21 is highly expressed in lingual epithelial cells and we have shown it acting in vitro to decrease the potency of bitterants on cultured cells. However, constitutive RGS21 loss in mice reduces organismal response to GPCR-mediated tastants—opposite to expectations arising from observed in vitro activity of RGS21 as a GAP and inhibitor of T2R signaling. Here, we show reduced quinine aversion and reduced sucrose preference by mice lacking RGS21 does not result from post-ingestive effects, as taste-salient brief-access tests confirm the reduced bitterant aversion and reduced sweetener preference seen using two-bottle choice testing. Eliminating Rgs21 expression after chemosensory system development, via tamoxifen-induced Cre recombination in eight week-old mice, led to a reduction in quinine aversive behavior that advanced over time, suggesting that RGS21 functions as a negative regulator to sustain stable bitter tastant reception. Consistent with this notion, we observed downregulation of multiple T2R proteins in the lingual tissue of Rgs21 -deficient mice. Reduced tastant-mediated responses exhibited by mice lacking Rgs21 expression either since birth or in adulthood has highlighted the potential requirement for a GPCR GAP to maintain the full character of tastant signaling, likely at the level of mitigating receptor downregulation. [ABSTRACT FROM AUTHOR]

We have characterized a recently rediscovered chemosensory structure at the rear of the mandibular mucosa in the mouse oral cavity originally reported in the 1980s. This consists of unorganized taste buds, not contained within troughs, associated with the ducts of an underlying minor salivary gland. Using whole-mount preparations of transgenic mice expressing green fluorescent protein under the promoter of taste-signaling-specific genes, we determined that the structure contains taste bud clusters and salivary gland orifices at the rear of each mandible, distal to the last molar and anterior to the ascending ramus. Immunohistochemical analysis shows in the retromolar taste buds expression of the taste receptors Tas2R131 and T1R3 and taste cascade molecules TrpM5, PLCβ2, and GNAT3, consistent with type II taste cells, and expression of GAD1, consistent with type III taste cells. Furthermore, the neuronal marker, calcitonin gene-related peptide, in retromolar mucosa tissue wrapping around TrpM5+ taste buds was observed. RT–PCR showed that retromolar taste buds express all 3 mouse tas1r genes, 28 of the 35 tas2r genes, and taste transduction signaling genes gnat3, plcb2 , and trpm5 , making the retromolar taste buds similar to other lingual and palate taste buds. Finally, histochemistry demonstrated that the mandibular retromolar secretory gland is a minor salivary gland of mucous type. The mandibular retromolar taste structure may thus play a role in taste sensation and represent a potential novel pharmacological target for taste disorders. [ABSTRACT FROM AUTHOR]

Sweet substances are detected by taste-bud cells upon binding to the sweet-taste receptor, a T1R2/T1R3 heterodimeric G protein-coupled receptor. In addition, experiments with mouse models lacking the sweet-taste receptor or its downstream signaling components led to the proposal of a parallel "alternative pathway" that may serve as metabolic sensor and energy regulator. Indeed, these mice showed residual nerve responses and behavioral attraction to sugars and oligosaccharides but not to artificial sweeteners. In analogy to pancreatic β cells, such alternative mechanism, to sense glucose in sweet-sensitive taste cells, might involve glucose transporters and KATP channels. Their activation may induce depolarization-dependent Ca2+ signals and release of GLP-1, which binds to its receptors on intragemmal nerve fibers. Via unknown neuronal and/or endocrine mechanisms, this pathway may contribute to both, behavioral attraction and/or induction of cephalic-phase insulin release upon oral sweet stimulation. Here, we critically review the evidence for a parallel sweet-sensitive pathway, involved signaling mechanisms, neural processing, interactions with endocrine hormonal mechanisms, and its sensitivity to different stimuli. Finally, we propose its physiological role in detecting the energy content of food and preparing for digestion. [ABSTRACT FROM AUTHOR]

Purinergic P2 receptors, activated by endogenous ATP, are prominently expressed on neuronal and non-neuronal cells during development of the auditory periphery and central auditory neurons. In the mature cochlea, extracellular ATP contributes to ion homeostasis, and has a protective function against noise exposure. Here, we focus on the modulation of activity by extracellular ATP during early postnatal development of the lower auditory pathway. In mammals, spontaneous patterned activity is conveyed along afferent auditory pathways before the onset of acoustically evoked signal processing. During this critical developmental period, inner hair cells fire bursts of action potentials that are believed to provide a developmental code for synaptic maturation and refinement of auditory circuits, thereby establishing a precise tonotopic organization. Endogenous ATP-release triggers such patterned activity by raising the extracellular K+ concentration and contributes to firing by increasing the excitability of auditory nerve fibers, spiral ganglion neurons, and specific neuron types within the auditory brainstem, through the activation of diverse P2 receptors. We review recent studies that provide new models on the contribution of purinergic signaling to early development of the afferent auditory pathway. Further, we discuss potential future directions of purinergic research in the auditory system. [ABSTRACT FROM AUTHOR]

Throughout the animal kingdom sucrose is one of the most palatable and preferred tastants. From an evolutionary perspective, this is not surprising as it is a primary source of energy. However, its overconsumption can result in obesity and an associated cornucopia of maladies, including type 2 diabetes and cardiovascular disease. Here we describe three physiological levels of processing sucrose that are involved in the decision to ingest it: the tongue, gut, and brain. The first section describes the peripheral cellular and molecular mechanisms of sweet taste identification that project to higher brain centers. We argue that stimulation of the tongue with sucrose triggers the formation of three distinct pathways that convey sensory attributes about its quality, palatability, and intensity that results in a perception of sweet taste. We also discuss the coding of sucrose throughout the gustatory pathway. The second section reviews how sucrose, and other palatable foods, interact with the gut–brain axis either through the hepatoportal system and/or vagal pathways in a manner that encodes both the rewarding and of nutritional value of foods. The third section reviews the homeostatic, hedonic, and aversive brain circuits involved in the control of food intake. Finally, we discuss evidence that overconsumption of sugars (or high fat diets) blunts taste perception, the post-ingestive nutritional reward value, and the circuits that control feeding in a manner that can lead to the development of obesity. [ABSTRACT FROM AUTHOR]

Gastrotricha is poor known phylum of small metazoans. Information about Ukrainian gastrotrichs' fauna is outdated. Althogether nine species are reported in this paper. Seven taxa are new to the fauna of Ukraine: Chaetonotus (Hystricochaetonotus) hystrix, Chaetonotus (Primochaetus) heideri, Chaetonotus (Zonochaeta) bisacer, Lepidodermella minor minor, Lepidodermella squamata, Ichthydium maximum and Haltidytes festinans. This investigation gives an additional morphological information on Chaetonotus (Chaetonotus) maximus and Chaetonotus (Hystricochaetonotus) macrochaetus, which have been earlier reported to the Ukraine fauna but currently they recorded in Kharkiv Region for the first time. We provide short morphological description of all species and give some ecological notes. [ABSTRACT FROM AUTHOR]

Studies have suggested that communication between taste cells shapes the gustatory signal before transmission to the brain. To further explore the possibility of intragemmal signal modulation, we adopted an optogenetic approach to stimulate sour-sensitive (Type III) taste cells using mice expressing Cre recombinase under a specific Type III cell promoter, Pkd2l1 (polycystic kidney disease-2-like 1), crossed with mice expressing Cre-dependent channelrhodopsin (ChR2). The application of blue light onto the tongue allowed for the specific stimulation of Type III cells and circumvented the nonspecific effects of chemical stimulation. To understand whether taste modality information is preprocessed in the taste bud before transmission to the sensory nerves, we recorded chorda tympani nerve activity during light and/or chemical tastant application to the tongue. To assess intragemmal modulation, we compared nerve responses to various tastants with or without concurrent light-induced activation of the Type III cells. Our results show that light significantly decreased taste responses to sweet, bitter, salty, and acidic stimuli. On the contrary, the light response was not consistently affected by sweet or bitter stimuli, suggesting that activation of Type II cells does not affect nerve responses to stimuli that activate Type III cells. [ABSTRACT FROM AUTHOR]

Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour, and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from internal stores in Type II cells when stimulated with bitter, sweet, or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCβ3-KO mouse confirmed that BR cells use this signaling pathway to respond to bitter, sweet, and umami stimuli. Short term behavioral assays revealed that BR cells make significant contributions to taste driven behaviors and found that loss of either PLCβ3 in BR cells or IP3R3 in Type II cells caused similar behavioral deficits to bitter, sweet, and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) also demonstrated that functional Type II and BR cells are required for normal stimulus induced expression. Author summary: We use our taste system to decide if we are going to consume or reject a potential food item. This is critical for survival, as we need energy to live but also need to avoid potentially toxic compounds. Therefore, it is important to understand how the taste cells in our mouth detect the chemicals in food and send a message to our brain. Signals from the taste cells form a code that conveys information about the nature of the potential food item to the brain. How this taste coding works is not well understood. Currently, it is thought that taste cells are primarily selective for each taste stimuli and only detect either bitter, sweet, sour, salt, or umami (amino acids) compounds. Our study describes a new population of taste cells that can detect multiple types of stimuli, including chemicals from different taste qualities. Thus, taste cells can be either selective or generally responsive to stimuli which is similar to the cells in the brain that process taste information. The presence of these broadly responsive taste cells provides new insight into how taste information is sent to the brain for processing. [ABSTRACT FROM AUTHOR]

Premature obesity-related mortality is caused by cardiovascular and pulmonary diseases, type 2 diabetes mellitus, physical disabilities, osteoarthritis, and certain types of cancer. Obesity is caused by a positive energy balance due to hyper-caloric nutrition, low physical activity, and energy expenditure. Overeating is partially driven by impaired homeostatic feedback of the peripheral energy status in obesity. However, food with its different qualities is a key driver for the reward driven hedonic feeding with tremendous consequences on calorie consumption. In addition to visual and olfactory cues, taste buds of the oral cavity process the earliest signals which affect the regulation of food intake, appetite and satiety. Therefore, taste buds may play a crucial role how food related signals are transmitted to the brain, particularly in priming the body for digestion during the cephalic phase. Indeed, obesity development is associated with a significant reduction in taste buds. Impaired taste bud sensitivity may play a causal role in the pathophysiology of obesity in children and adolescents. In addition, genetic variation in taste receptors has been linked to body weight regulation. This review discusses the importance of taste buds as contributing factors in the development of obesity and how obesity may affect the sense of taste, alterations in food preferences and eating behavior. [ABSTRACT FROM AUTHOR]

Cough is among the most common complaints for which patients worldwide seek medical attention. In a majority of patients with chronic cough (defined as cough of greater than 8 weeks' duration), successful management results from a thorough evaluation and treatment of underlying causes. In a subgroup of patients, however, cough proves refractory to therapeutic trials aimed at known reversible causes of chronic cough. Such patients are appropriately termed as having refractory chronic cough. At present, safe and effective medications are lacking for this challenging patient population. Currently available therapeutic options are usually ineffective or achieve antitussive effect at the expense of intolerable side effects, typically sedation. Fortunately, the past decade has witnessed great progress in elucidating underlying mechanisms of cough. From that knowledge, aided by the development of validated instruments to measure objective and subjective cough-related end points, numerous antitussive drug development programs have emerged. The most active area of inquiry at present involves antagonists of the purinergic P2X receptors. Indeed, four clinical programs (one in Phase 3 and three in Phase 2) are currently underway investigating antagonists of receptors comprised entirely or partially of the P2X3 subunit as potential antitussive medications. Herein we review the foundation on which P2X receptor antagonists were developed as potential antitussive medications and provide an update on current clinical trials. [ABSTRACT FROM AUTHOR]

Maternal body mass index and gestational weight gain predict future obesity status of the offspring. In studies of both rodents and non-human primates, maternal obesity also predicts a preference for palatable foods in the offspring. In this study, we used C57BL/6J mice to investigate whether an underlying cause for an increase in palatable food consumption in the offspring of obese mice was a change in taste function. Adult female mice were fed a normal chow (NC) or a high fat diet (HFD) for 5 weeks before mating, then also during the gestation (3 weeks) and lactation (3 weeks) periods, with offspring always maintained on a normal chow diet; thus the only experience offspring had with high fat food was via maternal exposure. Offspring exhibited similar weight, blood glucose levels and baseline water and chow intake in adulthood. Taste response was assessed after reaching maturity, using brief-access taste testing, with female offspring of obese dams showing an enhanced response to sucrose, and both sexes consuming more sucrose, sucralose and high fat diet if from obese mothers. Offspring also exhibited increased taste bud expression of mRNA for sweet receptor subunits T1R (Taste receptor type) 2 and 3, as well as other markers associated with taste signaling. Taste morphology in both groups appeared similar. Results indicate that obesity in the mother may lead to unhealthy feeding behavior in the offspring, correlating with altered expression of taste signaling elements, which likely drive increased avidity for palatable foods. [ABSTRACT FROM AUTHOR]

Trauma or neurodegenerative diseases trigger the retrograde death of retinal ganglion cells (RGCs), causing an irreversible functional loss. AT-rich interaction domain 1A (ARID1A), a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, has been shown to play crucial roles in cell homeostasis and tissue regeneration. However, its function in adult RGC regeneration remains elusive. Here, we show that optic nerve injury induces dynamic changes of Arid1a expression. Importantly, deleting Arid1a in mice dramatically promotes RGC survival, but insignificantly impacts axon regeneration after optic nerve injury. Next, joint profiling of transcripts and accessible chromatin in mature RGCs reveals that Arid1a regulates several genes involved in apoptosis and JAK/STAT signaling pathway. Thus, our findings suggest modulation of Arid1a as a potential therapeutic strategy to promote RGC neuroprotection after damage. [ABSTRACT FROM AUTHOR]