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."
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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.
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