Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Korea
Gene Expression Profile of Olfactory Transduction Signaling in an Animal Model of Human Multiple Sclerosis
Olfactory dysfunction occurs in multiple sclerosis in humans, as well as in an animal model of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyze differentially expressed genes (DEGs) in olfactory bulb of EAE-affected mice by next generation sequencing, with a particular focus on changes in olfaction-related signals. EAE was induced in C57BL/6 mice following immunization with myelin oligodendrocyte glycoprotein and adjuvant. Inflammatory lesions were identified in the olfactory bulbs as well as in the spinal cord of immunized mice. Analysis of DEGs in the olfactory bulb of EAE-affected mice revealed that 44 genes were upregulated (and which were primarily related to inflammatory mediators), while 519 genes were downregulated; among the latter, olfactory marker protein and stomatin-like 3, which have been linked to olfactory signal transduction, were significantly downregulated (log2 [fold change] >1 and p-value <0.05). These findings suggest that inflammation in the olfactory bulb of EAE-affected mice is associated with the downregulation of some olfactory signal transduction genes, particularly olfactory marker protein and stomatin-like 3, which may lead to olfactory dysfunction in an animal model of human multiple sclerosis.
https://link.springer.com/article/10.10 ... 014-9786-8
The essential trace element zinc plays a critical role in the regulation of immune homeostasis. Zinc deficiency or excess can cause severe impairment of the immune response, which points to the importance of the physiological and dietary control of zinc levels for a functioning immune system. We previously reported that injection of zinc aspartate suppresses experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), as well as effector T cell functions in vitro. Among the preferred characteristics of novel therapeutics for the treatment of autoimmune diseases such as MS are oral availability and a tolerable effective dose to minimize side effects. In this study, we investigated whether oral administration of zinc aspartate, an approved drug to treat zinc deficiency in humans, is effective in controlling EAE at clinically approved doses. We show that oral administration of 6 µg/day [0.3 mg/kg body weight (BW)] or 12 µg/day [0.6 mg/kg BW] of zinc aspartate reduces clinical and histopathological signs during the relapsing remitting phase of the disease in SJL mice. The clinical effect in mice was accompanied by suppression of IFN-γ, TNF-α, GM-CSF and IL-5 production in stimulated human T cells and mouse splenocytes in a dose-dependent manner. Furthermore, a large array of proinflammatory cytokines was modulated by zinc aspartate exposure in vitro. These data suggest that administration of oral zinc aspartate may have beneficial effects on autoimmune diseases like MS.
Here, we measured the zinc concentrations in the plasma of naive mice and of mice in the course of EAE and found a significant reduction of zinc plasma concentrations in mice with EAE on day 21 in comparison to zinc plasma concentrations of naive mice"
Olfactory function in zinc-deficient adult mice (1989)
"Adult zinc deficiency reportedly leads to degeneration of the olfactory epithelium in the rat. Human zinc deficiency can cause reduced olfactory sensitivity. Given the importance of zinc in embryonic neural development its primary action on the adult olfactory system may be to disrupt olfactory receptor neurogenesis. We report here on the effects of zinc deficiency on the olfactory system of the adult mouse. After 42 days of dietary restriction of zinc, mice were tested behaviourally for olfactory function and general activity. Their olfactory epithelia were examined histologically using [3H]-thymidine autoradiography to identify recently-divided cells, and immunohistochemistry for olfactory marker protein to identify mature receptor neurones. Zinc deficient mice failed to show a food odour preference but they Were as active as controls and their olfactory epithelia appeared normal. Basal cell proliferation and postmitotic survival were similar to controls and the epithelia were of normal thickness and were positive for olfactory marker protein. It was concluded that zinc deficiency did not affect the turnover of cells in the olfactory epithelium. It may disrupt olfactory function through interference with zinc-containing neurones in higher olfactory centres.
The evidence for zinc involvement in human olfaction is more equivocal. Acute serum zinc loss, induced by a few days of histidine treatment, was associated with raised odour detection and recognition thresholds in six patients. Administration of zinc quickly reversed these effects (Henkin et al. 1975). In contrast, a group of 106 patients with low serum zinc and smell
dysfunction secondary to a variety of etiological factors, were not helped by zinc sulphate treatment (Henkin et al. 1976).
The results indicate that zinc deficiency disrupted the sense of smell of adult mice."
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Department of Neurology, School of Medicine, University of Occupational and Environmental Healt, Japan
Olfactory identification associates with cognitive function and the third ventricle width in patients with relapsing-remitting multiple sclerosis.
Olfactory dysfunction is a known clinical feature of multiple sclerosis (MS). Some studies have shown that odor identification impairment is an essential feature associated with cognitive function in MS. This study investigates the relationship between olfactory identification and the disease state, including cognitive function and central brain volume, to evaluate the utility of olfactory identification in the clinical assessment of relapsing-remitting (RR) MS.
Forty patients with RRMS and 40 healthy controls (HCs) were included. Their olfactory identification was measured using the Odor Stick Identification Test for the Japanese (OSIT-J). Cognitive function was evaluated by the Japanese version of the Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III), and depressive mood was evaluated by the Center for Epidemiologic Studies Depression Scale. Magnetic resonance imaging was used to measure the third ventricle width (3rd VW) as a marker of central brain atrophy.
RRMS patients had a significantly lower OSIT-J score than HCs. The OSIT-J score was significantly lower in RRMS patients with low processing speed (PS) and working memory (WM) scores than RRMS patients with normal PS or WM scores. The OSIT-J score was significantly related to the PS, WM, and the 3rd VW. The OSIT-J score also showed a mild correlation with the expanded disability status scale and disease duration, but not with the number of clinical attacks or patient's age.
Our results suggest that olfactory identification impairment occurs in association with cognitive dysfunction and central brain atrophy. Thus, olfactory identification is a possible disease marker of RRMS as with cognitive impairment, especially PS, reflecting the diffuse neurodegeneration in RRMS.
Department of Neuroscience and Rehabilitation, University of Ferrara, Italy
Unraveling the Role of Dopaminergic and Calretinin Interneurons in the Olfactory Bulb
The perception and discriminating of odors are sensory activities that are an integral part of our daily life. The first brain region where odors are processed is the olfactory bulb (OB). Among the different cell populations that make up this brain area, interneurons play an essential role in this sensory activity. Moreover, probably because of their activity, they represent an exception compared to other parts of the brain, since OB interneurons are continuously generated in the postnatal and adult period. In this review, we will focus on periglomerular (PG) cells which are a class of interneurons found in the glomerular layer of the OB. These interneurons can be classified into distinct subtypes based on their neurochemical nature, based on the neurotransmitter and calcium-binding proteins expressed by these cells. Dopaminergic (DA) periglomerular cells and calretinin (CR) cells are among the newly generated interneurons and play an important role in the physiology of OB. In the OB, DA cells are involved in the processing of odors and the adaptation of the bulbar network to external conditions. The main role of DA cells in OB appears to be the inhibition of glutamate release from olfactory sensory fibers. Calretinin cells are probably the best morphologically characterized interneurons among PG cells in OB, but little is known about their function except for their inhibitory effect on noisy random excitatory signals arriving at the main neurons. In this review, we will mainly describe the electrophysiological properties related to the excitability profiles of DA and CR cells, with a particular view on the differences that characterize DA mature interneurons from cells in different stages of adult neurogenesis.
Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University,
Nasal Microbiota, Olfactory Health, Neurological Disorders and Aging-A Review
The nasal region is one of the distinct environments for the survival of various microbiota. The human microbial niche begins to inhabit the human body right from birth, and the microbiota survive as commensals or opportunistic pathogens throughout the life of humans in their bodies in various habitats. These microbial communities help to maintain a healthy microenvironment by preventing the attack of pathogens and being involved in immune regulation. Any dysbiosis of microbiota residing in the mucosal surfaces, such as the nasal passages, guts, and genital regions, causes immune modulation and severe infections. The coexistence of microorganisms in the mucosal layers of respiratory passage, resulting in infections due to their co-abundance and interactions, and the background molecular mechanisms responsible for such interactions, need to be considered for investigation. Additional clinical evaluations can explain the interactions among the nasal microbiota, nasal dysbiosis and neurodegenerative diseases (NDs). The respiratory airways usually act as a substratum place for the microbes and can act as the base for respiratory tract infections. The microbial metabolites and the microbes can cross the blood-brain barrier and may cause NDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis (MS). The scientific investigations on the potential role of the nasal microbiota in olfactory functions and the relationship between their dysfunction and neurological diseases are limited. Recently, the consequences of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in patients with neurological diseases are under exploration. The crosstalk between the gut and the nasal microbiota is highly influential, because their mucosal regions are the prominent microbial niche and are connected to the olfaction, immune regulation, and homeostasis of the central nervous system. Diet is one of the major factors, which strongly influences the mucosal membranes of the airways, gut, and lung. Unhealthy diet practices cause dysbiosis in gut microbiota and the mucosal barrier. The current review summarizes the interrelationship between the nasal microbiota dysbiosis, resulting olfactory dysfunctions, and the progression of NDs during aging and the involvement of coronavirus disease 2019 in provoking the NDs.
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