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Clinical Rheumatology Jan 2023Primary Sjögren's syndrome is an autoimmune exocrinopathy related to lymphocytic infiltration of the exocrine glandular epithelia (such as salivary, lacrimal, nasal,... (Review)
Review
Primary Sjögren's syndrome is an autoimmune exocrinopathy related to lymphocytic infiltration of the exocrine glandular epithelia (such as salivary, lacrimal, nasal, and sebaceous glands or vaginal mucosa) with systemic manifestations of an immuno-inflammatory nature, and not associated with any other systemic disease. It is characterized by severe dryness (Sicca syndrome), particularly in mouth and eyes, with potential strong impact on quality of life and could increase the risk of depression in Sjögren's patient. To date, the impairment of taste and olfactory functions related to Sjögren syndrome remains poorly assessed; so is the trigeminal functions which remain sparsely studied in patients with Sjögren disease. However, other factors can also modify chemosensory functions (olfactory or gustatory sensations and trigeminal nerves), in particular the reduction of the masticatory coefficient or halitosis, due to oral saliva flow decrease, and poor dental condition, which are often present in Sjögren patients. Of the 12 articles evaluated after a 22-year literature search of this review, chemosensory disorders (including taste, smell, and trigeminal impairments) are described and evaluated in pSS patients, with mainly poorer performance compared to healthy controls. Diagnostic and therapeutic (including rehabilitation) approaches of chemosensory disorders in pSS are discussed in this review. Clinician should be more attentive to taste as well as olfacto-trigeminal disorders in primary Sjögren's disease, if possible at the earlier stage, in order to take the best care of Sjögren's patients. This review also highlights some lack in knowledge on pSS chemosensory disorders that should provide new research perspectives. Key Points •Chemosensory functions (including taste, smell, and trigeminal functions) are altered in patients with primary Sjögren's syndrome (pSS) due to dryness of the mouth and the nose. •The trigeminal nerve which interacts with olfactory and gustatory nerves contributes to olfactory and taste perception but remains little studied to date. •Chemosensory function should be considered in the daily clinical assessment of patients with pSS. •Chemosensory function treatment is not standardized yet, however symptomatic treatment of Sjögren syndrome-associated dryness transiently would improve taste and smell, and olfactory or gustatory rehabilitation in pSS patients would be useful.
Topics: Female; Humans; Sjogren's Syndrome; Quality of Life; Saliva; Lacrimal Apparatus
PubMed: 36063255
DOI: 10.1007/s10067-022-06359-w -
Annual Review of Neuroscience Jul 2020Olfaction is fundamentally distinct from other sensory modalities. Natural odor stimuli are complex mixtures of volatile chemicals that interact in the nose with a...
Olfaction is fundamentally distinct from other sensory modalities. Natural odor stimuli are complex mixtures of volatile chemicals that interact in the nose with a receptor array that, in rodents, is built from more than 1,000 unique receptors. These interactions dictate a peripheral olfactory code, which in the brain is transformed and reformatted as it is broadcast across a set of highly interconnected olfactory regions. Here we discuss the problems of characterizing peripheral population codes for olfactory stimuli, of inferring the specific functions of different higher olfactory areas given their extensive recurrence, and of ultimately understanding how odor representations are linked to perception and action. We argue that, despite the differences between olfaction and other sensory modalities, addressing these specific questions will reveal general principles underlying brain function.
Topics: Animals; Brain; Humans; Nerve Net; Odorants; Olfactory Pathways; Olfactory Perception; Smell
PubMed: 32640927
DOI: 10.1146/annurev-neuro-102119-103452 -
Chemical Senses Jan 2023The presence of a perceptual bias due to anxiety is well demonstrated in cognitive and sensory task for the visual and auditory modality. Event-related potentials, by...
The presence of a perceptual bias due to anxiety is well demonstrated in cognitive and sensory task for the visual and auditory modality. Event-related potentials, by their specific measurement of neural processes, have strongly contributed to this evidence. There is still no consensus as to whether such a bias exists in the chemical senses; chemosensory event-related potentials (CSERPs) are an excellent tool to clarify the heterogeneous results, especially since the Late Positive Component (LPC) may be an indicator of emotional involvement after chemosensory stimulation. This research examined the association between state and trait anxiety and the amplitude and latency of pure olfactory and mixed olfactory-trigeminal LPC. In this study, 20 healthy participants (11 women) with a mean age of 24.6 years (SD = 2.6) completed a validated questionnaire to measure anxiety (STAI), and CSERP was recorded during 40 pure olfactory stimulations (phenyl ethanol) and 40 mixed olfactory-trigeminal stimulations (eucalyptol). LPC latency and amplitude were measured at Cz (electrode located at midline central) for each participant. We observed a significant negative correlation between LPC latencies and the state anxiety scores for the mixed olfactory-trigeminal condition (r(18) = -0.513; P = 0.021), but not for the pure olfactory condition. We did not observe any effect on LPC amplitudes. This study suggests that a higher level of state anxiety is related to a more rapid perceptual electrophysiological response for mixed olfactory-trigeminal stimuli but not for pure odors.
Topics: Adult; Female; Humans; Young Adult; Anxiety; Evoked Potentials; Odorants; Phenylethyl Alcohol; Smell; Trigeminal Nerve; Male
PubMed: 36976248
DOI: 10.1093/chemse/bjad010 -
Handbook of Clinical Neurology 2021The human vomeronasal organ (VNO) is an accessory olfactory organ located on the anteroinferior part of the nasal septum, 1.5-2.5cm from the nostrils. Its main role is... (Review)
Review
The human vomeronasal organ (VNO) is an accessory olfactory organ located on the anteroinferior part of the nasal septum, 1.5-2.5cm from the nostrils. Its main role is pheromone reception and, through its anatomical connections with the central nervous system, especially parts of the hypothalamus, modulation of both social and sexual behavior, although these relations have been established only in nonprimates and very little is yet established for the structure and function of the human VNO. Morphologically, the human VNO is a pit or duct-shaped structure, comprised of three cellular layers-basal cells, neural cells with olfactory cell morphology and immunohistochemical phenotype, and ciliated respiratory epithelium. Medially and connected to the VNO, a small nerve fiber is found that runs longitudinally to the nasal septum and is considered by some to be a distant process of the Cranial Nerve 0 or terminal nerve. In addition to pheromone reception, the human VNO has also been associated with several pathological conditions, including sinus septi nasi, posttraumatic stress disorder, and ectopic olfactory esthesioblastoma.
Topics: Humans; Nasal Cavity; Neuroanatomy; Nose; Smell; Vomeronasal Organ
PubMed: 34266599
DOI: 10.1016/B978-0-12-819973-2.00020-4 -
International Journal of Environmental... Jun 2021Research studies that focus on understanding the onset of neurodegenerative pathology and therapeutic interventions to inhibit its causative factors, have shown a... (Review)
Review
Research studies that focus on understanding the onset of neurodegenerative pathology and therapeutic interventions to inhibit its causative factors, have shown a crucial role of olfactory bulb neurons as they transmit and propagate nerve impulses to higher cortical and limbic structures. In rodent models, removal of the olfactory bulb results in pathology of the frontal cortex that shows striking similarity with frontal cortex features of patients diagnosed with neurodegenerative disorders. Widely different approaches involving behavioral symptom analysis, histopathological and molecular alterations, genetic and environmental influences, along with age-related alterations in cellular pathways, indicate a strong correlation of olfactory dysfunction and neurodegeneration. Indeed, declining olfactory acuity and olfactory deficits emerge either as the very first symptoms or as prodromal symptoms of progressing neurodegeneration of classical conditions. Olfactory dysfunction has been associated with most neurodegenerative, neuropsychiatric, and communication disorders. Evidence revealing the dual molecular function of the olfactory receptor neurons at dendritic and axonal ends indicates the significance of olfactory processing pathways that come under environmental pressure right from the onset. Here, we review findings that olfactory bulb neuronal processing serves as a marker of neuropsychiatric and neurodegenerative disorders.
Topics: Aging; Humans; Neurodegenerative Diseases; Neurons; Olfactory Bulb; Smell
PubMed: 34209997
DOI: 10.3390/ijerph18136976 -
Cells Nov 2022The central nervous system (CNS) has, among all organ systems in the human body, the highest failure rate of traditional small-molecule drug development, ranging from... (Review)
Review
The central nervous system (CNS) has, among all organ systems in the human body, the highest failure rate of traditional small-molecule drug development, ranging from 80-100% depending on the area of disease research. This has led to widespread abandonment by the pharmaceutical industry of research and development for CNS disorders, despite increased diagnoses of neurodegenerative disorders and the continued lack of adequate treatment options for brain injuries, stroke, neurodevelopmental disorders, and neuropsychiatric illness. However, new approaches, concurrent with the development of sophisticated bioinformatic and genomic tools, are being used to explore peptide-based therapeutics to manipulate endogenous pathways and targets, including "undruggable" intracellular protein-protein interactions (PPIs). The development of peptide-based therapeutics was previously rejected due to systemic off-target effects and poor bioavailability arising from traditional oral and systemic delivery methods. However, targeted nose-to-brain, or intranasal (IN), approaches have begun to emerge that allow CNS-specific delivery of therapeutics via the trigeminal and olfactory nerve pathways, laying the foundation for improved alternatives to systemic drug delivery. Here we review a dozen promising IN peptide therapeutics in preclinical and clinical development for neurodegenerative (Alzheimer's, Parkinson's), neuropsychiatric (depression, PTSD, schizophrenia), and neurodevelopmental disorders (autism), with insulin, NAP (davunetide), IGF-1, PACAP, NPY, oxytocin, and GLP-1 agonists prominent among them.
Topics: Humans; Pharmaceutical Preparations; Administration, Intranasal; Peptides; Drug Delivery Systems; Drug Development
PubMed: 36429060
DOI: 10.3390/cells11223629 -
Respiratory Physiology & Neurobiology May 2023Breathlessness is a centrally processed symptom, as evidenced by activation of distinct brain regions such as the insular cortex and amygdala, during the anticipation... (Review)
Review
Breathlessness is a centrally processed symptom, as evidenced by activation of distinct brain regions such as the insular cortex and amygdala, during the anticipation and/or perception of breathlessness. Inhaled L-menthol or blowing cool air to the face/nose, both selective trigeminal nerve (TGN) stimulants, relieve breathlessness without concurrent improvements in physiological outcomes (e.g., breathing pattern), suggesting a possible but hitherto unexplored central mechanism of action. Four databases were searched to identify published reports supporting a link between TGN stimulation and activation of brain regions involved in the anticipation and/or perception of breathlessness. The collective results of the 29 studies demonstrated that TGN stimulation activated 12 brain regions widely implicated in the anticipation and/or perception of breathlessness, including the insular cortex and amygdala. Inhaled L-menthol or cool air to the face activated 75% and 33% of these 12 brain regions, respectively. Our findings support the hypothesis that TGN stimulation contributes to breathlessness relief by altering the activity of brain regions involved in its central neural processing.
Topics: Humans; Olfactory Nerve; Menthol; Brain; Dyspnea; Perception; Trigeminal Nerve; Magnetic Resonance Imaging; Olfactory Perception
PubMed: 36804472
DOI: 10.1016/j.resp.2023.104036 -
Cell and Tissue Research Jan 2021The olfactory system is renowned for its functional and structural plasticity, with both peripheral and central structures displaying persistent neurogenesis throughout... (Review)
Review
The olfactory system is renowned for its functional and structural plasticity, with both peripheral and central structures displaying persistent neurogenesis throughout life and exhibiting remarkable capacity for regenerative neurogenesis after damage. In general, fish are known for their extensive neurogenic ability, and the zebrafish in particular presents an attractive model to study plasticity and adult neurogenesis in the olfactory system because of its conserved structure, relative simplicity, rapid cell turnover, and preponderance of neurogenic niches. In this review, we present an overview of the anatomy of zebrafish olfactory structures, with a focus on the neurogenic niches in the olfactory epithelium, olfactory bulb, and ventral telencephalon. Constitutive and regenerative neurogenesis in both the peripheral olfactory organ and central olfactory bulb of zebrafish is reviewed in detail, and a summary of current knowledge about the cellular origin and molecular signals involved in regulating these processes is presented. While some features of physiologic and injury-induced neurogenic responses are similar, there are differences that indicate that regeneration is not simply a reiteration of the constitutive proliferation process. We provide comparisons to mammalian neurogenesis that reveal similarities and differences between species. Finally, we present a number of open questions that remain to be answered.
Topics: Animals; Neurogenesis; Receptors, Odorant; Zebrafish
PubMed: 33245413
DOI: 10.1007/s00441-020-03334-2 -
Neuroscience and Biobehavioral Reviews Dec 2021The neuropeptide substance P (SP) plays an important role in neurodegenerative disorders, among which Parkinson's disease (PD). In the present work we have reviewed the... (Review)
Review
The neuropeptide substance P (SP) plays an important role in neurodegenerative disorders, among which Parkinson's disease (PD). In the present work we have reviewed the involvement of SP and its preferred receptor (NK1-R) in motor and non-motor PD symptoms, in both PD animal models and patients. Despite PD is primarily a motor disorder, non-motor abnormalities, including olfactory deficits and gastrointestinal dysfunctions, can represent diagnostic PD predictors, according to the hypothesis that the olfactory and the enteric nervous system represent starting points of neurodegeneration, ascending to the brain via the sympathetic fibers and the vagus nerve. In PD patients, the α-synuclein aggregates in the olfactory bulb and the gastrointestinal tract, as well as in the dorsal motor nucleus of the vagus nerve often co-localize with SP, indicating SP-positive neurons as highly vulnerable sites of degeneration. Considering the involvement of the SP/NK1-R in both the periphery and specific brain areas, this system might represent a neuronal substrate for the symptom and disease progression, as well as a therapeutic target for PD.
Topics: Animals; Brain; Gastrointestinal Tract; Humans; Parkinson Disease; Prognosis; Substance P; alpha-Synuclein
PubMed: 34653503
DOI: 10.1016/j.neubiorev.2021.10.008