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Neuropathology and Applied Neurobiology Apr 2024Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has... (Review)
Review
Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction.
Topics: Humans; COVID-19; SARS-CoV-2; Smell; Olfaction Disorders
PubMed: 38419211
DOI: 10.1111/nan.12960 -
Frontiers in Cellular Neuroscience 2023During early development, brains undergo profound changes in structure at the molecular, synaptic, cellular and circuit level. At the same time, brains need to perform... (Review)
Review
During early development, brains undergo profound changes in structure at the molecular, synaptic, cellular and circuit level. At the same time, brains need to perform adaptive function. How do structurally immature brains process information? How do brains perform stable and reliable function despite massive changes in structure? The rodent olfactory system presents an ideal model for approaching these poorly understood questions. Rodents are born deaf and blind, and rely completely on their sense of smell to acquire resources essential for survival during the first 2 weeks of life, such as food and warmth. Here, we review decades of work mapping structural changes in olfactory circuits during early development, as well as more recent studies performing electrophysiological recordings to characterize functional activity patterns generated by these circuits. The findings demonstrate that neonatal olfactory processing relies on an interacting network of brain areas including the olfactory bulb and piriform cortex. Circuits in these brain regions exhibit varying degrees of structural maturity in neonatal animals. However, despite substantial ongoing structural maturation of circuit elements, the neonatal olfactory system produces dynamic network-level activity patterns that are highly stable over protracted periods during development. We discuss how these findings inform future work aimed at elucidating the circuit-level mechanisms underlying information processing in the neonatal olfactory system, how they support unique neonatal behaviors, and how they transition between developmental stages.
PubMed: 37565031
DOI: 10.3389/fncel.2023.1225186 -
Acta Neuropathologica Communications May 2024The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs...
The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19 + patients.
Topics: Humans; COVID-19; Olfactory Bulb; Aged; Male; Female; Aged, 80 and over; Middle Aged; Microglia; alpha-Synuclein; tau Proteins; SARS-CoV-2; Neurodegenerative Diseases
PubMed: 38698465
DOI: 10.1186/s40478-024-01761-8 -
BMC Medicine Apr 2024ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown...
ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.
Topics: Humans; Animals; Mice; Abnormalities, Multiple; Intellectual Disability; Tooth Abnormalities; Bone Diseases, Developmental; Facies; Olfactory Bulb; Disease Models, Animal
PubMed: 38616269
DOI: 10.1186/s12916-024-03363-6 -
Frontiers in Neural Circuits 2024Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral... (Review)
Review
Various mammals have shown that sensory stimulation plays a crucial role in regulating the development of diverse structures, such as the olfactory bulb (OB), cerebral cortex, hippocampus, and retina. In the OB, the dendritic development of excitatory projection neurons like mitral/tufted cells is influenced by olfactory experiences. Odor stimulation is also essential for the dendritic development of inhibitory OB interneurons, such as granule and periglomerular cells, which are continuously produced in the ventricular-subventricular zone throughout life. Based on the morphological and molecular features, OB interneurons are classified into several subtypes. The role for each interneuron subtype in the control of olfactory behavior remains poorly understood due to lack of each specific marker. Among the several OB interneuron subtypes, a specific granule cell subtype, which expresses the oncofetal trophoblast glycoprotein (Tpbg or 5T4) gene, has been reported to be required for odor detection and discrimination behavior. This review will primarily focus on elucidating the contribution of different granule cell subtypes, including the Tpbg/5T4 subtype, to olfactory processing and behavior during the embryonic and adult stages.
Topics: Animals; Interneurons; Olfactory Bulb; Humans; Neurogenesis
PubMed: 38933598
DOI: 10.3389/fncir.2024.1427378 -
Current Opinion in Otolaryngology &... Feb 2024The purpose of this review is to summarize the recent literature relating to viral, fungal and bacterial infections and their interactions within the sinonasal tract in... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to summarize the recent literature relating to viral, fungal and bacterial infections and their interactions within the sinonasal tract in the past 18 months.
RECENT FINDINGS
Coronavirus disease 2019 (COVID-19)-associated olfactory dysfunction (OD) is variant dependent. Magnetic resonance imaging studies have found greater olfactory cleft opacification and higher olfactory bulb volume in post-COVID-19 OD. Olfactory training remains the mainstay of treatment, while platelet-rich plasma injections and ultramicronized palmitoylethanolamide and luteolin combination oral supplementation have shown early promise.Consensus statements on paranasal sinus fungal balls and acute invasive fungal sinusitis have been released.Studies on the nasal microbiome have reported Staphylococcus and Corynebacterium as the most abundant genera, with higher levels of Staphylococcus and Corynebacterium being found in patients with chronic rhinosinusitis (CRS) and healthy individuals respectively. However, there is conflicting evidence on the significance of biodiversity of the nasal microbiome found in CRS versus healthy patients.
SUMMARY
While the peak of the COVID-19 pandemic is behind us, its sequelae continue to pose treatment challenges. Further studies in OD have implications in managing the condition, beyond those afflicted post-COVID-19 infection. Similarly, more research is needed in studying the nasal microbiome and its implications in the development and treatment of CRS.
Topics: Humans; Pandemics; Paranasal Sinuses; Sinusitis; Chronic Disease; COVID-19; Communicable Diseases; Rhinitis
PubMed: 37997887
DOI: 10.1097/MOO.0000000000000947 -
Cell Reports Dec 2023Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial...
Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons to shape patterns of mitral cell firing that contribute to olfactory-related behaviors.
Topics: Mice; Animals; Olfactory Bulb; Smell; Dopamine; Interneurons; gamma-Aminobutyric Acid; Neurotransmitter Agents
PubMed: 37980561
DOI: 10.1016/j.celrep.2023.113471 -
Cancer Imaging : the Official... Oct 2023The glymphatic system actively exchanges cerebrospinal fluid (CSF) and interstitial fluid (ISF) to eliminate toxic interstitial waste solutes from the brain parenchyma....
BACKGROUND
The glymphatic system actively exchanges cerebrospinal fluid (CSF) and interstitial fluid (ISF) to eliminate toxic interstitial waste solutes from the brain parenchyma. Impairment of the glymphatic system has been linked to several neurological conditions. Glioblastoma, also known as Glioblastoma multiforme (GBM) is a highly aggressive form of malignant brain cancer within the glioma category. However, the impact of GBM on the functioning of the glymphatic system has not been investigated. Using dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) and advanced kinetic modeling, we examined the changes in the glymphatic system in rats with GBM.
METHODS
Dynamic 3D contrast-enhanced T1-weighted imaging (T1WI) with intra-cisterna magna (ICM) infusion of paramagnetic Gd-DTPA contrast agent was used for MRI glymphatic measurements in both GBM-induced and control rats. Glymphatic flow in the whole brain and the olfactory bulb was analyzed using model-derived parameters of arrival time, infusion rate, clearance rate, and residual that describe the dynamics of CSF tracer over time.
RESULTS
3D dynamic T1WI data identified reduced glymphatic influx and clearance, indicating an impaired glymphatic system due to GBM. Kinetic modeling and quantitative analyses consistently indicated significantly reduced infusion rate, clearance rate, and increased residual of CSF tracer in GBM rats compared to control rats, suggesting restricted glymphatic flow in the brain with GBM. In addition, our results identified compromised perineural pathway along the optic nerves in GBM rats.
CONCLUSIONS
Our study demonstrates the presence of GBM-impaired glymphatic response in the rat brain and impaired perineural pathway along the optic nerves. Reduced glymphatic waste clearance may lead to the accumulation of toxic waste solutes and pro-inflammatory signaling molecules which may affect the progression of the GBM.
Topics: Rats; Animals; Glioblastoma; Brain; Glymphatic System; Magnetic Resonance Imaging; Contrast Media
PubMed: 37904254
DOI: 10.1186/s40644-023-00628-w