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Neuroradiology Jan 2023The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction... (Meta-Analysis)
Meta-Analysis
PURPOSE
The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls.
METHODS
PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted.
RESULTS
Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators.
CONCLUSION
The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.
Topics: Humans; Olfaction Disorders; COVID-19; SARS-CoV-2; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 35843987
DOI: 10.1007/s00234-022-03014-8 -
International Journal of Molecular... Dec 2021Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the...
Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the influence of PM exposure on olfactory function must be investigated. In this study, we propose a zebrafish olfactory model to evaluate the effects of exposure to diesel particulate matter (DPM), which was labeled Korean diesel particulate matter (KDP20). KDP20 comprises heavy metals and polycyclic aromatic hydrocarbons (PAHs). KDP20 exposed olfactory organs exhibited reduced cilia and damaged epithelium. Olfactory dysfunction was confirmed using an odor-mediated behavior test. Furthermore, the olfactory damage was analyzed using Alcian blue and anti-calretinin staining. KDP20 exposed olfactory organs exhibited histological damages, such as increased goblet cells, decreased cell density, and calretinin level. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that PAHs exposure related genes ( and ) were upregulated. Reactive oxidation stress (ROS) () and inflammation () related genes were upregulated. Furthermore, olfactory sensory neuron (OSN) related genes ( and ) were downregulated. In conclusion, KDP20 exposure induced dysfunction of the olfactory system. Additionally, the zebrafish olfactory system exhibited a regenerative capacity with recovery conditions. Thus, this model may be used in future investigating PM-related diseases.
Topics: Aging; Animals; Behavior, Animal; Calbindin 2; Dynamic Light Scattering; Odorants; Olfactory Bulb; Particle Size; Particulate Matter; Spectrometry, X-Ray Emission; Survival Analysis; Vehicle Emissions; Zebrafish
PubMed: 35008830
DOI: 10.3390/ijms23010407 -
The Journal of Neuroscience : the... Jul 2002The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. The septum and the olfactory cortex have been shown...
The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. The septum and the olfactory cortex have been shown to secrete diffusible factors repelling olfactory axons in vitro and are likely to cause the axons to avoid the septum region in vivo. Slit2, a member of the Slit gene family, has been proposed to be this septal factor based on its expression in the embryonic septum and its ability to repel and collapse olfactory axons. However, this issue is still controversial, and recent in vitro studies have questioned the role of the septum and Slit proteins in organizing LOT projections. We therefore decided to examine directly the role of Slit proteins in mediating olfactory axon guidance in vivo using mice with targeted deletions in the Slit1 and Slit2 genes. When olfactory bulb explants are cocultured with septum from Slit1- and/or Slit2-deficient mice, the septum repulsive activity for olfactory bulb axons is progressively abolished in a gene dose-dependent manner. Anterograde tracing of olfactory bulb axons showed that the LOT develops normally in Slit1 or Slit2 single-deficient mice but is completely disorganized in Slit1/Slit2 double-deficient embryos, with many axons reaching the midline and entering the septum region. Therefore, our study showed that the septum chemorepellent is a combination of Slit1 and Slit2 and that these molecules play a significant role in olfactory bulb axon guidance in vivo.
Topics: Animals; Axons; COS Cells; Coculture Techniques; Intercellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Movement; Nerve Tissue Proteins; Olfactory Bulb; Olfactory Pathways; Septum of Brain
PubMed: 12097499
DOI: 10.1523/JNEUROSCI.22-13-05473.2002 -
The Journal of Comparative Neurology Oct 2011The olfactory peduncle, the region connecting the olfactory bulb with the basal forebrain, contains several neural areas that have received relatively little attention....
The olfactory peduncle, the region connecting the olfactory bulb with the basal forebrain, contains several neural areas that have received relatively little attention. The present work includes studies that provide an overview of the region in the mouse. An analysis of cell soma size in pars principalis (pP) of the anterior olfactory nucleus (AON) revealed considerable differences in tissue organization between mice and rats. An unbiased stereological study of neuron number in the cell-dense regions of pars externa (pE) and pP of the AON of 3-, 12-, and 24-month-old mice indicated that pE has about 16,500 cells in 0.043 mm(3) and pP about 58,300 cells in 0.307 mm(3) . Quantitative Golgi studies of pyramidal neurons in pP suggested that mouse neurons are similar to although smaller than those of the rat. An immunohistochemical analysis demonstrated that all peduncular regions (pE, pP, the dorsal peduncular cortex, ventral tenia tecta, and anterior olfactory tubercle and piriform cortex) have cells that express either calbindin, calretinin, parvalbumin, somatostatin, vasoactive intestinal polypeptide, neuropeptide Y, or cholecystokinin (antigens commonly co-expressed by subspecies of γ-aminobutyric acid [GABA]ergic neurons), although the relative numbers of each cell type differ between zones. Finally, an electron microscopic comparison of the organization of myelinated fibers in lateral olfactory tract in the anterior and posterior peduncle indicated that the region is less orderly in mice than in rats. The results provide a caveat for investigators who generalize data between species, as both similarities and differences between the laboratory mouse and rat were observed.
Topics: Animals; Cell Shape; Male; Mice; Mice, Inbred C57BL; Olfactory Bulb; Olfactory Pathways; Olfactory Receptor Neurons; Prosencephalon; Rats
PubMed: 21618219
DOI: 10.1002/cne.22662 -
Experimental Gerontology Aug 2017In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the... (Review)
Review
In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions.
Topics: Age Factors; Aging; Animals; Cell Movement; Cell Proliferation; Humans; Lateral Ventricles; Neural Stem Cells; Neurogenesis; Olfactory Bulb; Prosencephalon; Species Specificity; Stem Cell Niche
PubMed: 27867091
DOI: 10.1016/j.exger.2016.11.007 -
FEBS Letters Aug 2014Neuronal circuits in the olfactory bulb transform odor-evoked activity patterns across the input channels, the olfactory glomeruli, into distributed activity patterns... (Review)
Review
Neuronal circuits in the olfactory bulb transform odor-evoked activity patterns across the input channels, the olfactory glomeruli, into distributed activity patterns across the output neurons, the mitral cells. One computation associated with this transformation is a decorrelation of activity patterns representing similar odors. Such a decorrelation has various benefits for the classification and storage of information by associative networks in higher brain areas. Experimental results from adult zebrafish show that pattern decorrelation involves a redistribution of activity across the population of mitral cells. These observations imply that pattern decorrelation cannot be explained by a global scaling mechanism but that it depends on interactions between distinct subsets of neurons in the network. This article reviews insights into the network mechanism underlying pattern decorrelation and discusses recent results that link pattern decorrelation in the olfactory bulb to odor discrimination behavior.
Topics: Animals; Evoked Potentials, Somatosensory; Nerve Net; Neurons; Olfactory Bulb; Smell; Zebrafish
PubMed: 24911205
DOI: 10.1016/j.febslet.2014.05.055 -
Physiological Reports Nov 2019Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells....
Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells. These project to the primary olfactory cortex including the anterior olfactory nucleus (AON), the piriform cortex, amygdala, and the entorhinal cortex. The properties of mitral cells have been investigated extensively, but how odor information is processed in subsequent brain regions is less well known. In the present study, we recorded the electrical activity of AON neurons in anesthetized rats. Most AON cells fired in bursts of 2-10 spikes separated by very short intervals (<20 ms), in a period linked to the respiratory rhythm. Simultaneous recordings from adjacent neurons revealed that the rhythms of adjacent cells, while locked to the same underlying rhythm, showed marked differences in phase. We studied the responses of AON cells to brief high-frequency stimulation of the lateral olfactory tract, mimicking brief activation of mitral cells by odor. In different cells, such stimuli evoked transient or sustained bursts during stimulation or, more commonly, post-stimulation bursts after inhibition during stimulation. This suggests that, in AON cells, phase shifts occur as a result of post-inhibitory rebound firing, following inhibition by mitral cell input, and we discuss how this supports processing of odor information in the olfactory pathway. Cells were tested for their responsiveness to a social odor (the bedding of a strange male) among other simple and complex odors tested. In total, 11 cells responded strongly and repeatedly to bedding odor, and these responses were diverse, including excitation (transient or sustained), inhibition, and activation after odor presentation, indicating that AON neurons respond not only to the type of complex odor but also to temporal features of odor application.
Topics: Action Potentials; Animals; Electric Stimulation; Male; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Receptor Neurons; Rats; Rats, Sprague-Dawley
PubMed: 31782263
DOI: 10.14814/phy2.14284 -
The Journal of Neuroscience : the... Feb 2022The axon initial segment (AIS), nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the...
The axon initial segment (AIS), nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the faithful, coordinated transmission of action potentials (APs) to downstream brain regions. In the olfactory bulb (OB), olfactory discrimination tasks lead to adaptive changes in cell firing patterns, and the output signals must reliably travel large distances to other brain regions along highly myelinated tracts. Whether myelinated axons adapt to facilitate olfactory sensory processing is unknown. Here, we investigate the morphology and physiology of mitral cell (MC) axons in the olfactory system of adult male and female mice and show that unilateral sensory deprivation causes system-wide adaptations in axonal morphology and myelin thickness. MC spiking patterns and APs also adapted to sensory deprivation. Strikingly, myelination and MC physiology were altered on both the deprived and nondeprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system. Successful transmission of information from the olfactory bulb (OB) to piriform cortex through the lateral olfactory tract (LOT) relies on synchronized arrival of action potentials (APs). The coincident arrival of APs is dependent on reliable generation of APs in the axon initial segment (AIS) and fast conduction mediated by axon myelination. Here, we studied changes in mitral cell (MC) firing and AIS structure as well as changes in myelination of the LOT on unilateral olfactory deprivation in the adult mouse. Strikingly, myelination and MC physiology were altered on both the deprived and nondeprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system.
Topics: Animals; Axons; Female; Male; Mice; Myelin Sheath; Olfactory Bulb; Sensory Deprivation; Smell
PubMed: 35022219
DOI: 10.1523/JNEUROSCI.0305-21.2021 -
PloS One 2017Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory...
Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.
Topics: Adolescent; Adult; Aged; Brain Diseases; Case-Control Studies; Female; Herpesvirus 6, Human; Humans; Male; Microglia; Middle Aged; Neurons; Olfactory Bulb; Roseolovirus Infections
PubMed: 28072884
DOI: 10.1371/journal.pone.0170071 -
Nature Communications Jan 2020Current non-invasive neuroimaging methods can assess neural activity in all areas of the human brain but the olfactory bulb (OB). The OB has been suggested to fulfill a...
Current non-invasive neuroimaging methods can assess neural activity in all areas of the human brain but the olfactory bulb (OB). The OB has been suggested to fulfill a role comparable to that of V1 and the thalamus in the visual system and have been closely linked to a wide range of olfactory tasks and neuropathologies. Here we present a method for non-invasive recording of signals from the human OB with millisecond precision. We demonstrate that signals obtained via recordings from EEG electrodes at the nasal bridge represent responses from the human olfactory bulb - recordings we term Electrobulbogram (EBG). The EBG will aid future olfactory-related translational work but can also potentially be implemented as an everyday clinical tool to detect pathology-related changes in human central olfactory processing in neurodegenerative diseases. In conclusion, the EBG is localized to the OB, is reliable, and follows response patterns demonstrated in non-human animal models.
Topics: Adult; Electroencephalography; Female; Humans; Male; Olfactory Bulb; Young Adult
PubMed: 32005822
DOI: 10.1038/s41467-020-14520-9