Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance

Disrupted systemic copper (Cu) homeostasis underlies neurodegenerative diseases with early symptoms including olfactory dysfunction. This study investigated the impact of Cu dyshomeostasis on olfactory function, adult neurogenesis, and neurochemical balance. Models of Cu deficiency (CuD) and Cu overload (CuO) were established by feeding adult rats with Cu-restricted diets plus ip. injection of a Cu chelator (ammonium tetrathiomolybdate) and excess Cu, respectively. CuD reduced Cu levels in the olfactory bulb (OB), subventricular zone (SVZ), rostral migratory stream (RMS), and striatum, while CuO increased Cu levels in these areas. The buried pellet test revealed both CuD and CuO prolonged the latency to uncover food. CuD increased neural proliferation and stem cells in the SVZ and newly differentiated neurons in the OB, whereas CuO caused opposite alterations, suggesting a “switch”-type function of Cu in regulating adult neurogenesis. CuO increased GABA in the OB, while both CuD and CuO reduced DOPAC, HVA, 5-HT and the DA turnover rate in olfactory-associated brain regions. Altered mRNA expression of Cu transport and storage proteins in tested brain areas were observed under both conditions. Together, results support an association between systemic Cu dyshomeostasis and olfactory dysfunction. Specifically, altered adult neurogenesis along the SVZ-RMS-OB pathway and neurochemical imbalance could be the factors that may contribute to olfactory dysfunction.

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Does COVID-19 Affect Adult Neurogenesis? A Neurochemical Perspective

10.5772/intechopen.101179 ◽

2021 ◽

Author(s):

Jayakumar Saikarthik ◽

Ilango Saraswathi ◽

Abdulrahman A. Al-Atram

Keyword(s):

Adult Neurogenesis ◽

Cell Activation ◽

Immune Cell ◽

Neuropsychiatric Symptoms ◽

Brain Regions ◽

Immune Cell Activation ◽

Brain Involvement ◽

The Impact ◽

The Brain

COVID-19 has been found to cause neuropsychiatric symptoms which indicate brain involvement. SARS-CoV-2 may enter the brain by damaging and penetrating olfactory mucosa and via other possible routes like damaged blood–brain barrier, and hematologic spread. With SARS-CoV-2 having a higher affinity to ACE2 receptors, brain regions that have higher ACE2 receptors like the hippocampus, are more vulnerable to the effect of the viral invasion. In addition, immune cell activation, an important feature of COVID-19, leads to cytokine storm which causes neurotoxicity, neuroinflammation, and neurodegeneration. Impaired adult neurogenesis is related to many psychiatric disorders including depression, bipolar disorder, anxiety disorder, schizophrenia, and PTSD. It is known to be related to the depletion of neurotransmitters, dopamine, serotonin, norepinephrine, GABA, and glutamate which play a major role in adult neurogenesis. A recent study reveals that SSRI which acts by increasing serotonin is proven beneficial in COVID-19 patients. Thus, the current chapter will discuss the impact of COVID-19 on adult neurogenesis with emphasis on the role of ACE2 and neurotransmitters.

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The Impact Of Chronic Rhinosinusitis On Olfaction: Immunohistochemical Study

QJM ◽

10.1093/qjmed/hcaa047.009 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

Y F Elbeltagy ◽

H S Elhalabi ◽

N S Ahmed ◽

A M Maarouf ◽

M F Saleeb

Keyword(s):

Chronic Rhinosinusitis ◽

Olfactory Dysfunction ◽

Olfactory Mucosa ◽

Olfactory Function ◽

Specific Marker ◽

Intermediate Filament Protein ◽

Nestin Expression ◽

Protein Marker ◽

Significant Difference ◽

The Impact

Abstract Background Chronic rhinosinusitis (CRS) is one of the leading causes of olfactory. Olfactory impairments in CRS can be classified into two broad mechanisms of impairment: conductive losses from obstruction of the nasal passages, or sensorineural causes from damage to the olfactory neuroepithelium. Nestin is one type of intermediate filament protein, was a specific marker for OE stem cells. It was found that nestin is actually expressed in the axonal ends and inferior processes of OE sustentacular cells in the basal compartment of the epithelium. Nestin immunoreactivity, which is clearly present in the sustentacular cell layer of normosmic patients, was slightly reduced in the OE of subjects suffering from hyposmia. In contrast, in the OE of anosmics, nestin expression was found to be noticeably reduced. This indicates that expression of nestin protein is related to olfactory function and is down regulated with loss of olfactory function. Methods This study included 60 patients (20 chronic rhinosinusitis with polyps patients (CRSwp), 20 chronic rhinosinusitis without polyps patients (CRSsp), and 20 controls). Biopsies taken from olfactory mucosa during surgery. Immunohistochemical examination was done using nestin protein marker, a marker directly related to function in olfactory mucosa, to examine the etiology of olfactory dysfunction in CRS. Results There was a significant difference between the three study groups was found regarding olfaction. While there was a highly statistically significant difference between the three groups regarding nestin staining pattern, however, when comparing the two cases groups, the difference was not significant. Nestin staining decreased in both cases groups and patients with CRSwp have more olfactory dysfunction than patients with CRSsp. This means that while the inflammatory process is strongly present in both groups, the presence of polyps increases olfactory function loss. Conclusion Olfactory dysfunction in patients with CRS is multifactorial where both obstructive and inflammatory causes contribute in the pathogenesis.

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Impacts of Perinatal Induced Photothrombotic Stroke on Sensorimotor Performance in Adult Rats

Physiological Research ◽

10.33549/physiolres.932447 ◽

2013 ◽

pp. 85-94 ◽

Cited By ~ 5

Author(s):

T. BRIMA ◽

A. MIKULECKÁ ◽

J. OTÁHAL

Keyword(s):

Ischemic Stroke ◽

Motor Function ◽

Motor Performance ◽

Functional Performance ◽

Morphological Changes ◽

Volume Ratio ◽

Brain Regions ◽

Adult Rats ◽

The Impact ◽

Exposition Time

Perinatal ischemic stroke is a leading cerebrovascular disorder occurring in infants around the time of birth associated with long term comorbidities including motor, cognitive and behavioral deficits. We sought to determine the impact of perinatal induced stroke on locomotion, behavior and motor function in rats. A photothrombotic model of ischemic stroke was used in rat at postnatal day 7. Presently, we induced two lesions of different extents, to assess the consequences of stroke on motor function, locomotion and possible correlations to morphological changes. Behavioral tests sensitive to sensorimotor changes were used; locomotion expressed as distance moved in the open field was monitored and histological changes were also assessed. Outcomes depicted two kinds of lesions of different shapes and sizes, relative to laser illumination. Motor performance of rats submitted to stroke was poor when compared to controls; a difference in motor performance was also noted between rats with small and large lesions. Correlations were observed between: motor performance and exposition time; volume ratio and exposition time; and in the rotarod between motor performance and volume ratio. Outcomes demonstrate that photothrombotic cerebral ischemic stroke induced in early postnatal period and tested in adulthood, indeed influenced functional performance governed by the affected brain regions.

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Recovery of Olfactory Function in Postviral Olfactory Dysfunction Patients after Acupuncture Treatment

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/4986034 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Qi Dai ◽

Zhihui Pang ◽

Hongmeng Yu

Keyword(s):

Olfactory Dysfunction ◽

Olfactory Function ◽

University Of Pennsylvania ◽

Observation Group ◽

Olfactory Test ◽

Standardized Treatment ◽

Duration Of Disease ◽

The University ◽

The Impact ◽

Smell Identification

Introduction. The aims of this study were to assess the impact of traditional Chinese acupuncture (TCA) in postviral olfactory dysfunction (PVOD) patients who were refractory to standardized treatment and to compare the results with the impact observed in an observation group.Methods. Fifty patients who presented to the outpatient clinic with PVOD and were refractory to standardized treatment were included: 25 were treated with TCA and 25 patients were simply observed. A subjective olfactory test was performed using the University of Pennsylvania Smell Identification Test (UPSIT). The effects of TCA were compared with the results obtained in the observation group.Results. Improved olfactory function was observed in eleven patients treated with TCA compared with four patients in the observation group. This study revealed significantly improved olfactory function outcomes in patients who underwent acupuncture compared with the observation group. No significant differences in olfaction recovery were found according to age, gender, or duration of disease between the two groups; however, hyposmic patients recovered at a higher rate than anosmic patients.Conclusion. TCA may aid the treatment of PVOD patients who are refractory to drugs or other therapies.

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High toluene exposure risk increases risk of olfactory dysfunction in furniture workers

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2015.v34.68-76 ◽

2016 ◽

Vol 34 (1) ◽

pp. 68

Author(s):

Magdalena Wartono ◽

Herkutanto Herkutanto ◽

Niken Lestari

Keyword(s):

Occupational Exposure ◽

Negative Impact ◽

Cross Sectional Study ◽

Olfactory Dysfunction ◽

Olfactory Function ◽

Exposure Level ◽

Potential Hazard ◽

Cross Sectional ◽

Toluene Exposure ◽

The Impact

BACKGROUND Few studies have investigated the impact on olfactory functioning of occupational exposure to toluene, an industrial solvent used in paints and cleaning fluids. The estimated olfactory dysfunction prevalence is 0.5– 5%. Patients frequently do not complain about olfactory dysfunction. However, occupational exposure to chemicals may affect workers’ health and safety, because of their continuous inhalation. This study aimed to examine the relationship between toluene exposure and olfactory dysfunction in furniture workers. METHODS This was a cross-sectional study involving 65 workers. Data collection was by observation and interview on demographic characteristics, history of habits, and symptoms of chronic rhinitis. Risk of exposure scores were evaluated from potential hazard, exposure level, duration of employment, type of work, use of masks, ventilation of work space, and education and training. Olfactory function was tested using Sniffin’ Sticks, and determination of environmental toluene level was by personal sampling. The odds ratio was used to test correlations between variables. RESULTS Only 44 subjects could be analyzed, 37 (84.1%) of whom had olfactory dysfunction. Workers with high toluene exposure had a significantly 12.5- fold risk of olfactory dysfunction in comparison with those with low exposure (OR=12.5; CI 95% 1.35 – 115.79). CONCLUSIONS Toluene exposure increases risk of olfactory dysfunction in furniture workers. Olfactory function testing should be considered for initial screening or periodic testing of furniture workers. Low toluene levels with a high proportion of olfactory dysfunction indicate that olfactory dysfunction is an early negative impact of chemical inhalation.

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High toluene exposure risk increases risk of olfactory dysfunction in furniture workers

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2015.v34.68-72 ◽

2016 ◽

Vol 34 (1) ◽

pp. 68

Author(s):

Magdalena Wartono ◽

Herkutanto Herkutanto ◽

Niken Lestari

Keyword(s):

Occupational Exposure ◽

Negative Impact ◽

Cross Sectional Study ◽

Olfactory Dysfunction ◽

Olfactory Function ◽

Exposure Level ◽

Potential Hazard ◽

Cross Sectional ◽

Toluene Exposure ◽

The Impact

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The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

The Natural Products Journal ◽

10.2174/2210315509666190723131511 ◽

2020 ◽

Vol 10 (5) ◽

pp. 578-586

Author(s):

Areeg M. Abdelrazek ◽

Shimaa A. Haredy

Keyword(s):

Oxidative Stress ◽

Coenzyme Q10 ◽

Protective Role ◽

Albino Rats ◽

Distilled Water ◽

Negative Effects ◽

Adult Rats ◽

Stress Damage ◽

The Impact ◽

Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

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The Impact of Alkaloid-Producing Epichloë Endophyte on Forage Ryegrass Breeding: A New Zealand Perspective

Toxins ◽

10.3390/toxins13020158 ◽

2021 ◽

Vol 13 (2) ◽

pp. 158

Author(s):

Colin Eady

Keyword(s):

Seed Production ◽

Health Issues ◽

Abiotic Stressors ◽

Livestock Health ◽

The Right ◽

The Impact ◽

The Relationship ◽

And Storage ◽

Selection Of ◽

Epichloë Endophyte

For 30 years, forage ryegrass breeding has known that the germplasm may contain a maternally inherited symbiotic Epichloë endophyte. These endophytes produce a suite of secondary alkaloid compounds, dependent upon strain. Many produce ergot and other alkaloids, which are associated with both insect deterrence and livestock health issues. The levels of alkaloids and other endophyte characteristics are influenced by strain, host germplasm, and environmental conditions. Some strains in the right host germplasm can confer an advantage over biotic and abiotic stressors, thus acting as a maternally inherited desirable ‘trait’. Through seed production, these mutualistic endophytes do not transmit into 100% of the crop seed and are less vigorous than the grass seed itself. This causes stability and longevity issues for seed production and storage should the ‘trait’ be desired in the germplasm. This makes understanding the precise nature of the relationship vitally important to the plant breeder. These Epichloë endophytes cannot be ‘bred’ in the conventional sense, as they are asexual. Instead, the breeder may modulate endophyte characteristics through selection of host germplasm, a sort of breeding by proxy. This article explores, from a forage seed company perspective, the issues that endophyte characteristics and breeding them by proxy have on ryegrass breeding, and outlines the methods used to assess the ‘trait’, and the application of these through the breeding, production, and deployment processes. Finally, this article investigates opportunities for enhancing the utilisation of alkaloid-producing endophytes within pastures, with a focus on balancing alkaloid levels to further enhance pest deterrence and improving livestock outcomes.

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Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection

Biomedicines ◽

10.3390/biomedicines9030287 ◽

2021 ◽

Vol 9 (3) ◽

pp. 287

Author(s):

Maria Isabella Donegani ◽

Alberto Miceli ◽

Matteo Pardini ◽

Matteo Bauckneht ◽

Silvia Chiola ◽

...

Keyword(s):

Fdg Pet ◽

Structural Connectivity ◽

Statistical Parametric Mapping ◽

Brain Regions ◽

Olfactory Dysfunction ◽

Whole Body ◽

Mapping Software ◽

18F Fdg ◽

Left Insula

We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [18F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19.

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Postinfectious Olfactory Dysfunction: Oral Steroids and Olfactory Training versus Olfactory Training Alone: Is There any Benefit from Steroids?

ORL ◽

10.1159/000516316 ◽

2021 ◽

pp. 1-8

Author(s):

Sotiria Genetzaki ◽

Evangelia Tsakiropoulou ◽

Vasilios Nikolaidis ◽

Konstantinos Markou ◽

Iordanis Konstantinidis

Keyword(s):

Olfactory Dysfunction ◽

Olfactory Function ◽

Line Treatment ◽

First Line ◽

Olfactory Testing ◽

Significant Difference ◽

Oral Steroids ◽

Group A ◽

Olfactory Training ◽

First Line Treatment

Introduction: There are limited treatment options for postinfectious olfactory dysfunction (PIOD). Olfactory training has recently been used in clinical practice, but no medical treatment is widely accepted. Although there is weak evidence for their value, some physicians use oral corticosteroids as first-line treatment. The aim of this study was to compare combined oral methylprednisolone and olfactory training with olfactory training alone in the management of PIOD. Methods: This prospective cohort study included 131 patients with PIOD over a 2-year period before the COVID-19 pandemic. Seventy-eight patients who were treated with oral methylprednisolone and olfactory training (group A) were compared with 53 patients who were treated with olfactory training only (group B). Olfactory function was evaluated with “Sniffin’ Sticks” at baseline and 2, 8, and 16 weeks after initial assessment. Patients who improved after steroid treatment underwent magnetic resonance imaging of the paranasal sinuses, skin prick tests, lung spirometry, and sputum eosinophil assessment. Results: Oral steroids improved 19.23% of patients (n = 15) of group A. History, clinical evaluation, imaging, and laboratory tests identified an inflammatory background in half of them (n = 8). The remaining 7 had no findings of nasal inflammation, and all had a short history of olfactory dysfunction. Both groups significantly improved in olfactory testing results at the end of the olfactory training scheme without significant difference between them. Conclusions: The percentage of improved patients after oral methylprednisolone was relatively low to suggest it as first-line treatment. Half of the improved patients had an underlying upper airway inflammatory condition not related to the infection that caused the acute loss of olfactory function.

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