-
Journal of Neurology Mar 2023Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVE
Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated yet. Brain MR imaging is a consolidated method for evaluating olfactory system's morphological modification, but a few quantitative studies have been published so far. The aim of the study was to provide MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms, including olfactory dysfunction.
METHODS
196 COVID-19 patients (median age: 53 years, 56% females) and 39 controls (median age 55 years, 49% females) were included in this cross-sectional observational study; 78 of the patients reported olfactory loss as the only neurological symptom. MRI processing was performed by ad-hoc semi-automatic processing procedures. Olfactory bulb (OB) volume was measured on T2-weighted MRI based on manual tracing and normalized to the brain volume. Olfactory tract (OT) median signal intensity was quantified on fluid attenuated inversion recovery (FLAIR) sequences, after preliminary intensity normalization.
RESULTS
COVID-19 patients showed significantly lower left, right and total OB volumes than controls (p < 0.05). Age-related OB atrophy was found in the control but not in the patient population. No significant difference was found between patients with olfactory disorders and other neurological symptoms. Several outliers with abnormally high OT FLAIR signal intensity were found in the patient group.
CONCLUSIONS
Brain MRI findings demonstrated OB damage in COVID-19 patients with neurological complications. Future longitudinal studies are needed to clarify the transient or permanent nature of OB atrophy in COVID-19 pathology.
Topics: Female; Humans; Middle Aged; Male; COVID-19; Cross-Sectional Studies; Olfaction Disorders; Smell; Magnetic Resonance Imaging; Olfactory Bulb
PubMed: 36656356
DOI: 10.1007/s00415-023-11561-0 -
Brain Pathology (Zurich, Switzerland) May 2016The olfactory bulb with its unique architecture was studied for neuronal maturation in human fetuses. Neuroblasts stream into the olfactory bulb from the rostral...
The olfactory bulb with its unique architecture was studied for neuronal maturation in human fetuses. Neuroblasts stream into the olfactory bulb from the rostral telencephalon and secondarily migrate radially. The transitory olfactory ventricular recess regresses postnatally. Olfactory is the only sensory system without thalamic projections but incorporates intrinsic thalamic equivalents. The bulb is a repository of progenitor cells. Maturation of the bulb and tract was studied in 18 normal human fetuses of 16-41 weeks gestation; mid-gestational twins with hydrocephalus; 7 arrhinencephaly/holoprosencephaly; 2 olfactory dysgeneses. Multiple immunoreactivities were performed. Synaptophysin around mitral neurons, in a few synaptic glomeruli and concentric lamination of the outer granular layer, was seen at 16 weeks. Outer granular neurons exhibited NeuN at 16 weeks, only 2/3 were reactive at term. Concentric alternating sheets of granular neurons and their dendrodendritic synapses are seen during maturation. Calretinin reactivity is seen in neurons and neurites, primary olfactory nerve axons, periglomerular cells and neuroepithelial cells surrounding the ventricular recess; reactivity occurs later in synaptic glomeruli than with synaptophysin; not all glomeruli are strongly reactive even at term. Nestin- and vimentin-reactive bipolar progenitor cells were demonstrated at all ages and extend into the olfactory tract. Myelin is demonstrated by Luxol fast blue (LFB) only postnatally. In hydrocephalus, the olfactory recess is dilated. Mitral cell dispersion, disrupted glomeruli, heterotopia and maturational delay are seen in some dysgeneses. Malformations exhibit unique findings. Fusion of hypoplastic bulbs can occur. Abnormal architecture is seen in hemimegalencephaly. More documentation of olfactory dysgenesis is needed in other major brain malformations.
Topics: Fetus; Humans; Neurogenesis; Olfactory Bulb
PubMed: 26096058
DOI: 10.1111/bpa.12275 -
Diagnostic and Interventional Radiology... Mar 2023Olfactory dysfunction is a well-known complication in epilepsy. Studies have demonstrated that olfactory bulb volume (OBV), olfactory tract length (OTL), and olfactory...
PURPOSE
Olfactory dysfunction is a well-known complication in epilepsy. Studies have demonstrated that olfactory bulb volume (OBV), olfactory tract length (OTL), and olfactory sulcus depth (OSD) can be reliably evaluated using magnetic resonance imaging (MRI). In this study, we compared the OBV, OTL, and OSD values of children with epilepsy and those of healthy children (controls) of similar age. Our aim was to determine the presence of olfactory dysfunction in children with epilepsy and demonstrate the effects of the epilepsy type and treatment on olfactory function in these patients.
METHODS
Cranial MRI images of 36 patients with epilepsy and 108 controls (3-17 years) were evaluated. The patients with epilepsy were divided into groups according to the type of disease and treatment method. Subsequently, OBV and OSD were measured from the coronal section and OTL from the sagittal section. The OBV, OTL, and OSD values were compared between the epilepsy group, subgroups, and controls.
RESULTS
OBV was significantly reduced in the children with epilepsy compared with the control group ( < 0.001). No significant difference between the healthy children and those with epilepsy was determined in terms of OTL and OSD. Although OBV was moderately positively correlated with age in the control group (r = 0.561, < 0.001), it was poorly correlated with age in children with epilepsy (r = 0.393, = 0.018).
CONCLUSION
The results of our study indicate that OBV decreases in children with epilepsy, but epilepsy type and treatment method do not affect OBV, OTL, or OSD ( > 0.05).
Topics: Humans; Child; Magnetic Resonance Imaging; Epilepsy; Olfactory Bulb; Olfaction Disorders
PubMed: 36988051
DOI: 10.5152/dir.2022.21287 -
Neuron Aug 2010Odor signals received by odorant receptors (ORs) in the olfactory epithelium are represented as an odor map of activated glomeruli in the olfactory bulb. In the mouse... (Review)
Review
Odor signals received by odorant receptors (ORs) in the olfactory epithelium are represented as an odor map of activated glomeruli in the olfactory bulb. In the mouse olfactory system, it appears that much of axon pathfinding and sorting occurs autonomously by olfactory neuron axons. Here, we review the recent progress on the study of olfactory map formation in rodents. We will discuss how neuronal identity is represented at axon termini and how the OR-instructed axonal projection is regulated.
Topics: Animals; Mice; Models, Neurological; Olfactory Bulb; Olfactory Pathways; Olfactory Receptor Neurons
PubMed: 20797531
DOI: 10.1016/j.neuron.2010.07.003 -
The Anatomical Record Feb 2002The peripheral olfactory system is able to recover after injury, i.e., the olfactory epithelium reconstitutes, the olfactory nerve regenerates, and the olfactory bulb is... (Review)
Review
The peripheral olfactory system is able to recover after injury, i.e., the olfactory epithelium reconstitutes, the olfactory nerve regenerates, and the olfactory bulb is reinnervated, with a facility that is unique within the mammalian nervous system. Cell renewal in the epithelium is directed to replace neurons when they die in normal animals and does so at an accelerated pace after damage to the olfactory nerve. Neurogenesis persists because neuron-competent progenitor cells, including transit amplifying and immediate neuronal precursors, are maintained within the population of globose basal cells. Notwithstanding events in the neuron-depleted epithelium, the death of both non-neuronal cells and neurons directs multipotent globose basal cell progenitors, to give rise individually to sustentacular cells and horizontal basal cells as well as neurons. Multiple growth factors, including TGF-alpha, FGF2, BMPs, and TGF-betas, are likely to be central in regulating choice points in epitheliopoiesis. Reinnervation of the bulb is rapid and robust. When the nerve is left undisturbed, i.e., by lesioning the epithelium directly, the projection of the reconstituted epithelium onto the bulb is restored to near-normal with respect to rhinotopy and in the targeting of odorant receptor-defined neuronal classes to small clusters of glomeruli in the bulb. However, at its ultimate level, i.e., the convergence of axons expressing the same odorant receptor onto one or a few glomeruli, specificity is not restored unless a substantial number of fibers of the same type are spared. Rather, odorant receptor-defined subclasses of neurons innervate an excessive number of glomeruli in the rough vicinity of their original glomerular targets.
Topics: Animals; Axons; Cell Lineage; Nerve Regeneration; Olfactory Bulb; Olfactory Mucosa; Olfactory Nerve; Olfactory Nerve Injuries; Receptors, Odorant
PubMed: 11891623
DOI: 10.1002/ar.10047 -
Proceedings of the National Academy of... Mar 2018Olfaction is an important sensory modality driving fundamental behaviors. During odor-dependent learning, a positive value is commonly assigned to an odorant, and...
Olfaction is an important sensory modality driving fundamental behaviors. During odor-dependent learning, a positive value is commonly assigned to an odorant, and multiple forms of plasticity are involved when such odor-reward associations are formed. In rodents, one of the mechanisms underlying plasticity in the olfactory bulb consists in recruiting new neurons daily throughout life. However, it is still unknown whether adult-born neurons might participate in encoding odor value. Here, we demonstrate that exposure to reward-associated odors specifically increases activity of adult-born neurons but not preexisting neurons. Remarkably, adult-born neuron activation during rewarded odor presentation heightens discrimination learning and enhances the ability to update the odor value during reversal association. Moreover, in some cases, activation of this interneuron population can trigger olfactory learning without sensory stimulation. Taken together, our results show a specific involvement of adult-born neurons in facilitating odor-reward association during adaptive learning.
Topics: Animals; Discrimination Learning; Female; Male; Models, Neurological; Odorants; Olfactory Bulb; Olfactory Receptor Neurons; Rats; Reward; Smell
PubMed: 29467284
DOI: 10.1073/pnas.1716400115 -
Frontiers in Neural Circuits 2013The clever choice of animal models has been instrumental for many breakthrough discoveries in life sciences. One of the outstanding challenges in neuroscience is the... (Review)
Review
The clever choice of animal models has been instrumental for many breakthrough discoveries in life sciences. One of the outstanding challenges in neuroscience is the in-depth analysis of neuronal circuits to understand how interactions between large numbers of neurons give rise to the computational power of the brain. A promising model organism to address this challenge is the zebrafish, not only because it is cheap, transparent and accessible to sophisticated genetic manipulations but also because it offers unique advantages for quantitative analyses of circuit structure and function. One of the most important advantages of zebrafish is its small brain size, both at larval and adult stages. Small brains enable exhaustive measurements of neuronal activity patterns by optical imaging and facilitate large-scale reconstructions of wiring diagrams by electron microscopic approaches. Such information is important, and probably essential, to obtain mechanistic insights into neuronal computations underlying higher brain functions and dysfunctions. This review provides a brief overview over current methods and motivations for dense reconstructions of neuronal activity and connectivity patterns. It then discusses selective advantages of zebrafish and provides examples how these advantages are exploited to study neuronal computations in the olfactory bulb.
Topics: Animals; Brain; Humans; Models, Animal; Nerve Net; Neurons; Olfactory Bulb; Zebrafish
PubMed: 23630467
DOI: 10.3389/fncir.2013.00071 -
The Journal of Neuroscience : the... Mar 2007The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. It is known that the septum secretes Slit1 and... (Comparative Study)
Comparative Study
The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. It is known that the septum secretes Slit1 and Slit2 which repel olfactory axons in vitro and that in Slit1-/-;Slit2-/- mutant mice, the LOT is profoundly disrupted. However, the involvement of Slit receptors, the roundabout (Robo) proteins, in guiding LOT axons has not been demonstrated. We show here that both Robo1 and Robo2 receptors are expressed on early developing LOT axons, but that only Robo2 is present at later developmental stages. Olfactory bulb axons from Robo1-/-;Robo2-/- double-mutant mice are not repelled by Slit in vitro. The LOT develops normally in Robo1-/- mice, but is completely disorganized in Robo2-/- and Robo1-/-;Robo2-/- double-mutant embryos, with many LOT axons spreading along the ventral surface of the telencephalon. Finally, the position of lot1-expressing cells, which have been proposed to be the LOT guidepost cells, appears unaffected in Slit1-/-;Slit2-/- mice and in Robo1-/-;Robo2-/- mice. Together, our results indicate that Robo1 and Robo2 directly mediate the repulsive activity of Slit receptors on LOT axons, and are required for normal guidance of these axons in vivo.
Topics: Animals; Humans; Mice; Mice, Knockout; Mice, Transgenic; Nerve Tissue Proteins; Olfactory Bulb; Olfactory Pathways; Receptors, Immunologic; Roundabout Proteins
PubMed: 17360927
DOI: 10.1523/JNEUROSCI.0172-07.2007 -
Annals of the New York Academy of... Jul 2009The adult mammalian brain continuously generates new neurons in the olfactory bulb and hippocampus throughout life. Adult neurogenesis, a highly dynamic process, has... (Review)
Review
The adult mammalian brain continuously generates new neurons in the olfactory bulb and hippocampus throughout life. Adult neurogenesis, a highly dynamic process, has been shown to be exquisitely modulated by neuronal circuit activity at different stages, from proliferation of adult neural progenitors, to differentiation, maturation, integration, and survival of newborn neurons in the adult brain. Strategic activity-dependent addition of new neurons into the existing neuronal circuitry represents a prominent form of structural plasticity and may contribute to specific brain functions, such as learning, memory, and mood modulation. Here we review extrinsic mechanisms through which adult neurogenesis is regulated by environmental cues, physiological learning-related stimuli, and neuronal activities.
Topics: Animals; Hippocampus; Mice; Neurogenesis; Olfactory Bulb
PubMed: 19686209
DOI: 10.1111/j.1749-6632.2009.04373.x -
ENeuro 2019The inter-regional connectivity of sensory structures in the brain allows for the modulation of sensory processing in manners important for perception. In the olfactory...
The inter-regional connectivity of sensory structures in the brain allows for the modulation of sensory processing in manners important for perception. In the olfactory system, odor representations in the olfactory bulb (OB) are modulated by feedback centrifugal innervation from several olfactory cortices, including the piriform cortex (PCX) and anterior olfactory nucleus (AON). Previous studies reported that an additional olfactory cortex, the olfactory tubercle (OT), also centrifugally innervates the OB and may even shape the activity of OB output neurons. In an attempt to identify the cell types of this centrifugal innervation, we performed retrograde tracing experiments in mice utilizing three unique strategies, including retrobeads, retrograde adeno-associated virus (AAV) driving a fluorescent reporter, and retrograde AAV driving Cre-expression in the Ai9-floxed transgenic reporter line. Our results replicated the standing literature and uncovered robustly labeled neurons in the ipsilateral PCX, AON, and numerous other structures known to innervate the OB. Surprisingly, consistent throughout all of our approaches, no labeled soma were observed in the OT. These findings indicate that the OT is unique among other olfactory cortices in that it does not innervate the OB, which refines our understanding of the centrifugal modulation of the OB.
Topics: Animals; Female; Male; Mice, Inbred C57BL; Mice, Transgenic; Neuroanatomical Tract-Tracing Techniques; Olfactory Bulb; Olfactory Pathways
PubMed: 30740517
DOI: 10.1523/ENEURO.0390-18.2019