Re-Print Cell Impact: Pathophysiological Mechanism of Sars-Cov-2 in the Olfactory and Gustatory System

Smell and taste alterations are very common in patients with COVID 19, even when we are in an asymptomatic phase of the disease, it is reported that up to 80 to 90% of patients present anosmia and ageusia as a cardinal symptom of the disease. In this manuscript we will mention the alterations and the mode of action of the Sars-cov-2 virus at the level of the nasal and buccal fossae, taking into account the alterations at the cellular level as a result of this, based on current evidence, remembering that it is still unknown. A lot about this disease and the way this virus works.

Drosophila Central Taste Circuits in Health and Obesity

When there is a perturbation in the balance between hunger and satiety, food intake gets mis-regulated leading to excessive or insufficient eating. In humans, abnormal nutrient consumption causes metabolic conditions like obesity, diabetes, and eating disorders affecting overall health. Despite this burden on society, we currently lack enough knowledge about the neuronal circuits that regulate appetite and taste perception. How specific taste neuronal circuits influence feeding behaviours is still an under explored area in neurobiology. The taste information present at the periphery must be processed by the central circuits for the final behavioural output. Identification and understanding of central neural circuitry regulating taste behaviour and its modulation by physiological changes with regard to internal state is required to understand the neural basis of taste preference. Simple invertebrate model organisms like Drosophila melanogaster can sense the same taste stimuli as mammals. Availability of powerful molecular and genetic tool kit and well characterized peripheral gustatory system with a vast array of behavioural, calcium imaging, molecular and electrophysiological approaches make Drosophila an attractive system to investigate and understand taste wiring and processing in the brain. By exploiting the gustatory system of the flies, this chapter will shed light on the current understanding of central neural taste structures that influence feeding choices. The compiled information would help us better understand how central taste neurons convey taste information to higher brain centers and guide feeding behaviours like acceptance or rejection of food to better combat disease state caused by abnormal consumption of food.

Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.

Salivary Digestion Extends the Range of Sugar-Aversions in the German Cockroach

Saliva has diverse functions in feeding behavior of animals. However, the impact of salivary digestion of food on insect gustatory information processing is poorly documented. Glucose-aversion (GA) in the German cockroach, Blattella germanica, is a highly adaptive heritable behavioral resistance trait that protects the cockroach from ingesting glucose-containing-insecticide-baits. In this study, we confirmed that GA cockroaches rejected glucose, but they accepted oligosaccharides. However, whereas wild-type cockroaches that accepted glucose also satiated on oligosaccharides, GA cockroaches ceased ingesting the oligosaccharides within seconds, resulting in significantly lower consumption. We hypothesized that saliva might hydrolyze oligosaccharides, releasing glucose and terminating feeding. By mixing artificially collected cockroach saliva with various oligosaccharides, we demonstrated oligosaccharide-aversion in GA cockroaches. Acarbose, an alpha-glucosidase inhibitor, prevented the accumulation of glucose and rescued the phagostimulatory response and ingestion of oligosaccharides. Our results indicate that pre-oral and oral hydrolysis of oligosaccharides by salivary alpha-glucosidases released glucose, which was then processed by the gustatory system of GA cockroaches as a deterrent and caused the rejection of food. We suggest that the genetic mechanism of glucose-aversion support an extended aversion phenotype that includes glucose-containing oligosaccharides. Salivary digestion protects the cockroach from ingesting toxic chemicals and thus could support the rapid evolution of behavioral and physiological resistance in cockroach populations.

Salivary Digestion Extends the Range of Sugar-Aversions in the German Cockroach

Saliva has diverse functions in feeding behavior of animals. However, the impact of salivary digestion of food on insect gustatory information processing is poorly documented. Glucose-aversion (GA) in the German cockroach, Blattella germanica, is a highly adaptive heritable behavioral resistance trait that protects the cockroach from ingesting glucose-containing-insecticide-baits. In this study, we confirmed that GA cockroaches rejected glucose, but they accepted oligosaccharides. However, whereas wild-type cockroaches that accepted glucose also satiated on oligosaccharides, GA cockroaches ceased ingesting the oligosaccharides within seconds, resulting in significantly lower consumption. We hypothesized that saliva might hydrolyze oligosaccharides, releasing glucose and terminating feeding. By mixing artificially collected cockroach saliva with various oligosaccharides, we demonstrated oligosaccharide-aversion in GA cockroaches. Acarbose, an alpha-glucosidase inhibitor, prevented the accumulation of glucose and rescued the phagostimulatory response and ingestion of oligosaccharides. Our results indicate that pre-oral and oral hydrolysis of oligosaccharides by salivary alpha-glucosidases released glucose, which was then processed by the gustatory system of GA cockroaches as a deterrent and caused the rejection of food. We suggest that the genetic mechanism of glucose-aversion support an extended aversion phenotype that includes glucose-containing oligosaccharides. Salivary digestion protects the cockroach from ingesting toxic chemicals and thus could support the rapid evolution of behavioral and physiological resistance in cockroach populations.

Taste Buds and Gustatory Transduction: A Functional Perspective

Everything a person swallows must pass a final chemical analysis by the sensory systems of the mouth; of these, the gustatory system is cardinal. Gustation can be heuristically divided into three basic domains of function: sensory-discriminative (quality and intensity), motivational/affective (promote or deter ingestion), and physiological (e.g., salivation and insulin release). The signals from the taste buds, transmitted to the brain through the sensory branches of cranial nerves VII (facial), IX (glossopharyngeal), and X (vagal), subserve these primary functions. Taste buds are collections of 50–100 cells that are distributed in various fields in the tongue, soft palate, and throat. There are three types of cells that have been identified in taste buds based on their morphological and cytochemical expression profiles. Type II cells express specialized G-protein-coupled receptors (GPCR or GPR) on their apical membranes, which protrude through a break in the oral epithelial lining called the taste pore, that are responsible for the sensing of sweeteners (via the taste type 1 receptor (T1R) 2 + T1R3), amino acids (via the T1R1+T1R3), and bitter ligands (via the taste type 2 receptors (T2Rs)). Type III cells are critical for the sensing of acids via the otopetrin-1 (Otop-1) ion channel. The sensing of sodium, in at least rodents, occurs through the epithelial sodium channel (ENaC), but the exact composition of this channel and the type of taste cell type in which the functional version resides remains unclear. It is controversial whether Type I cells, which have been characterized as glial-like, are involved in sodium transduction or play any taste signaling role. For the most part, receptors for different stimulus classes (e.g., sugars vs. bitter ligands) are not co-expressed, providing significant early functionally related segregation of signals. There remains a persistent search for yet to be identified receptors that may contribute to some functions associated with stimuli representing the so-called basic taste qualities—sweet, salty, sour, bitter, and umami—as well as unconventional stimuli such as fatty acids (in addition to cluster of differentiation-36 (CD-36), GPR40, and GPR120) and maltodextrins. The primary neurotransmitter in taste receptor cells is ATP, which is released through a voltage-gated heteromeric channel consisting of the calcium homeostasis modulator 1 and 3 (CALHM1/3) and binds with P2X2/X3 receptors on apposed afferent fibers. Serotonin released from Type III cells has been implicated as an additional neurotransmitter, binding with HT3a receptors, and possibly playing a role in acid taste (which is sour to humans). Taste bud cells undergo complete turnover about every two weeks. Although there remains much to be understood about the operations of the taste bud, perhaps the one very clear principle that emerges is that the organization of signals transmitted to the brain is not random and arbitrary to be decoded by complex algorithms in the circuits of the central gustatory system. Rather, the transmission of taste information from the periphery is highly ordered.

Anatomical Organization and Coding in the Gustatory System: A Functional Perspective

Gustatory signals from the mouth travel to the rostral nucleus of the solitary tract (rNST) over the VIIth (anterior tongue and palate) and IXth (posterior tongue) cranial nerves and synapse in the central subdivision in an overlapping orotopic pattern. Oral somatosensory information likewise reaches rNST, preferentially terminating in the lateral subdivision. Two additional rNST subdivisions, the medial and ventral, receive only sparse primary afferent inputs. Ascending pathways arise primarily from the central subdivision; local reflex and intranuclear pathways originate from the other subdivisions. Thus, parallel processing is already evident at the first central nervous system (CNS) relay. Ascending rNST taste fibers connect to the pontine parabrachial nucleus (PBN), strongly terminating in the ventral lateral (VL) and medial subnuclei (M) of the waist region but also in the external lateral (EL) and medial (EM) subnuclei. PBN projections travel along two main routes. A “lemniscal” processing stream connects to the thalamic taste relay, the parvicellular division of the ventroposteromedial nucleus (VPMpc), which in turn projects to insular cortex. A second, “limbic” pathway synapses in the lateral hypothalamus (LH), central nucleus of the amygdala (CeA), bed nucleus of the stria terminalis (BNST), and substantia innominata (SI). The ventral tegmental area (VTA), a critical nucleus in the so-called reward circuit, also receives input from the gustatory PBN. Forebrain gustatory structures are interconnected and give rise to copious feedback pathways. Single-neuron recording and calcium imaging demonstrates that taste response profiles in both the peripheral nerves and CNS lemniscal structures are highly orderly. Arguably, a limited number of neuron “types” are defined by the qualitative class of compounds (sugars, sweeteners, amino acids, sodium salts, acids and non-sodium salts, “bitter”) that elicit the largest response in a cell. In the periphery and NST, some findings suggest these classes correspond to distinct molecular phenotypes and functions, but evidence for a cortical chemotopic organization is highly controversial. CNS neuron types are complicated by convergence and lability as a function of homeostatic, cognitive, and experiential variables. Moreover, gustatory responses are dynamic, providing additional coding potential in the temporal domain. Interestingly, taste responses in the limbic pathway are particularly plastic and code for hedonics more obviously than quality. Studies in decerebrate rats reveal that the brainstem is sufficient to maintain appropriate oromotor and somatic responses, referred to as taste reactivity, to nutritive (sugars) and harmful (quinine) stimuli. However, forebrain processing is necessary for taste reactivity to be modulated by learning, at least with respect to taste aversion conditioning. Functional studies of the rodent cortex tell a complex story. Lesion studies in rats emphasize a considerable degree of residual function in animals lacking large regions of insular cortex despite demonstrating shifts in detection thresholds for certain, but not all, stimuli representing different taste qualities. They also have an impact on conditioned taste aversion. Investigations in mice employing optogenetic and chemogenetic manipulations suggest that different regions of insular cortex are critical for discriminating certain qualities and that their connections to the amygdala underlie their hedonic impact. The continued use of sophisticated behavioral experiments coordinated with molecular methods for monitoring and manipulating activity in defined neural circuits should ultimately yield satisfying answers to long-standing debates about the fundamental operation of the gustatory system.

Neural Coding of Food Is a Multisensory, Sensorimotor Function

This review is a curated discussion of the relationship between the gustatory system and the perception of food beginning at the earliest stage of neural processing. A brief description of the idea of taste qualities and mammalian anatomy of the taste system is presented first, followed by an overview of theories of taste coding. The case is made that food is encoded by the several senses that it stimulates beginning in the brainstem and extending throughout the entire gustatory neuraxis. In addition, the feedback from food-related movements is seamlessly melded with sensory input to create the representation of food objects in the brain.