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Cell Transplantation 2011Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush... (Review)
Review
Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush and nerve disruption defects. Transplantation of myelin-forming cells, such as Schwann cells (SCs) or olfactory ensheathing cells (OECs), may be beneficial to the regenerative process because the applied cells could mediate neurotrophic and neuroprotective effects by secretion of chemokines. Moreover, myelin-forming cells are capable of bridging the repair site by establishing an environment permissive to axonal regeneration. The cell types that are subject to intense investigation include SCs and OECs either derived from the olfactory bulb or the olfactory mucosa, stromal cells from bone marrow (mesenchymal stem cells, MSCs), and adipose tissue-derived cells. OECs reside in the peripheral and central nervous system and have been suggested to display unique regenerative properties. However, so far OECs were mainly used in experimental studies to foster central regeneration and it was not until recently that their regeneration-promoting activity for the peripheral nervous system was recognized. In the present review, we summarize recent experimental evidence regarding the regenerative effects of OECs applied to the peripheral nervous system that may be relevant to design novel autologous cell transplantation therapies.
Topics: Animals; Cell Transplantation; Humans; Nerve Regeneration; Olfactory Bulb; Peripheral Nerve Injuries; Wound Healing
PubMed: 20719095
DOI: 10.3727/096368910X522081 -
Current Biology : CB Jun 2011High-resolution tracing of projections from the olfactory bulb to its cortical targets revealed coarse topography and stereotopy in some areas but highly distributed,...
High-resolution tracing of projections from the olfactory bulb to its cortical targets revealed coarse topography and stereotopy in some areas but highly distributed, combinatorial connectivity in others. These results provide a basis for understanding innate and associative olfactory processing and perception.
Topics: Animals; Mice; Neuroanatomical Tract-Tracing Techniques; Neurosciences; Olfactory Bulb; Olfactory Pathways; Olfactory Perception; Olfactory Receptor Neurons
PubMed: 21640905
DOI: 10.1016/j.cub.2011.04.036 -
NeuroImage Oct 2019Laminar organization of neuronal circuits is a recurring feature of how the brain processes information. For instance, different layers compartmentalize different cell... (Review)
Review
Laminar organization of neuronal circuits is a recurring feature of how the brain processes information. For instance, different layers compartmentalize different cell types, synaptic activities, and have unique intrinsic and extrinsic connections that serve as units for specialized signal processing. Functional MRI is an invaluable tool to investigate laminar processing in the in vivo human brain, but it measures neuronal activity indirectly by way of the hemodynamic response. Therefore, the accuracy of high-resolution laminar fMRI depends on how precisely it can measure localized microvascular changes nearest to the site of evoked activity. To determine the specificity of fMRI responses to the true neurophysiological responses across layers, the flexibility to invasive procedures in animal models has been necessary. In this review, we will examine different fMRI contrasts and their appropriate uses for layer-specific fMRI, and how localized laminar processing was examined in the neocortex and olfactory bulb. Through collective efforts, it was determined that microvessels, including capillaries, are regulated within single layers and that several endogenous and contrast-enhanced fMRI contrast mechanisms can separate these neural-specific vascular changes from the nonspecific, especially cerebral blood volume-weighted fMRI with intravenous contrast agent injection. We will also propose some open questions that are relevant for the successful implementation of layer-specific fMRI and its potential future directions to study laminar processing when combined with optogenetics.
Topics: Animals; Functional Neuroimaging; Magnetic Resonance Imaging; Models, Animal; Neocortex; Neurovascular Coupling; Olfactory Bulb
PubMed: 28502845
DOI: 10.1016/j.neuroimage.2017.05.023 -
AJNR. American Journal of Neuroradiology Oct 2020Unique among the acute neurologic manifestations of Severe Acute Respiratory Syndrome coronavirus 2, the virus responsible for the coronavirus disease 2019 (COVID-19)...
BACKGROUND AND PURPOSE
Unique among the acute neurologic manifestations of Severe Acute Respiratory Syndrome coronavirus 2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, is chemosensory dysfunction (anosmia or dysgeusia), which can be seen in patients who are otherwise oligosymptomatic or even asymptomatic. The purpose of this study was to determine if there is imaging evidence of olfactory apparatus pathology in patients with COVID-19 and neurologic symptoms.
MATERIALS AND METHODS
A retrospective case-control study compared the olfactory bulb and olfactory tract signal intensity on thin-section T2WI and postcontrast 3D T2 FLAIR images in patients with COVID-19 and neurologic symptoms, and age-matched controls imaged for olfactory dysfunction.
RESULTS
There was a significant difference in normalized olfactory bulb T2 FLAIR signal intensity between the patients with COVID-19 and the controls with anosmia ( = .003). Four of 12 patients with COVID-19 demonstrated intraneural T2 signal hyperintensity on postcontrast 3D T2 FLAIR compared with none of the 12 patients among the controls with anosmia ( = .028).
CONCLUSIONS
Olfactory bulb 3D T2 FLAIR signal intensity was greater in the patients with COVID-19 and neurologic symptoms compared with an age-matched control group with olfactory dysfunction, and this was qualitatively apparent in 4 of 12 patients with COVID-19. Analysis of these preliminary finding suggests that olfactory apparatus vulnerability to COVID-19 might be supported on conventional neuroimaging and may serve as a noninvasive biomarker of infection.
Topics: Aged; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Olfactory Bulb; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2
PubMed: 32855190
DOI: 10.3174/ajnr.A6751 -
Current Biology : CB Apr 2021Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics,...
Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics, we report here that stimulating the representation of pleasant odorants in a sensory structure, the pOB, can be rewarding, self-motivating, and is accompanied by ventral tegmental area activation. To explore the underlying neural circuitry downstream of the olfactory bulb (OB), we use 3D high-resolution imaging and optogenetics and determine that the pOB preferentially projects to the olfactory tubercle, whose increased activity is related to odorant attraction. We further show that attractive odorants act as reinforcers in dopamine-dependent place preference learning. Finally, we extend those findings to humans, who exhibit place preference learning and an increase BOLD signal in the olfactory tubercle in response to attractive odorants. Thus, strong and persistent attraction induced by some odorants is due to a direct gateway from the pOB to the reward system.
Topics: Animals; Emotions; Male; Mice; Mice, Inbred C57BL; Motivation; Odorants; Olfactory Bulb; Olfactory Perception; Optogenetics; Reward; Smell
PubMed: 33607032
DOI: 10.1016/j.cub.2021.01.066 -
Journal of Virology Sep 2018Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more...
Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences. Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.
Topics: Animals; Axons; Coronavirus Infections; Coronavirus OC43, Human; Humans; Mice; Nasal Cavity; Olfactory Bulb; Piriform Cortex; Viral Proteins; Virus Assembly
PubMed: 29925652
DOI: 10.1128/JVI.00404-18 -
G3 (Bethesda, Md.) Mar 2019Olfaction mediates behaviors necessary for survival and reproduction in fishes. Anthropogenic inputs of contaminants into aquatic environments, specifically copper, are...
Olfaction mediates behaviors necessary for survival and reproduction in fishes. Anthropogenic inputs of contaminants into aquatic environments, specifically copper, are known to disrupt a broad range of olfactory-mediated behaviors and can cause long-lasting damage even at low concentrations that have profound impacts on the biology of aquatic organisms. The sea lamprey ( is a primitive fish species invasive to the North American Great Lakes that relies on olfaction to navigate during natal homing and in mate choice during reproduction. To investigate effects of copper on sea lamprey olfaction and the potential for maintenance of olfactory function during copper exposure, we exposed juvenile sea lamprey to environmentally ecologically relevant copper concentrations (0, 5, 10 and 30 µg/L) for 24 hr and characterized gene transcription response in olfactory tissue (, peripheral olfactory organ and olfactory bulb) and forebrain using whole transcriptome sequencing. Copper exposure induced a pattern of positive dose-dependent transcriptional response. Expression changes primarily reflected up-regulation of genes involved in apoptosis and wound healing. Unlike higher vertebrates, genes specifically related to the olfactory senses of the sea lamprey, , olfactory receptors, exhibited little transcriptional response to copper exposure, suggesting the mechanism of copper-induced olfactory impairment is through necrosis of the olfactory bulb and not copper-selective inhibition of olfactory receptors. Fully two-thirds of the differentially expressed genes at higher doses of copper have no known function and thus represent important candidates for further study of the responses to copper-induced olfactory injury. Our results shed light on the evolution of vertebrate olfactory repair mechanisms and have important implications for the conservation and management of both invasive and native populations of lamprey.
Topics: Animals; Copper; Gene Expression Regulation; Olfactory Bulb; Petromyzon; Transcription, Genetic; Transcriptome
PubMed: 30670609
DOI: 10.1534/g3.118.200920 -
International Forum of Allergy &... Nov 2018Idiopathic olfactory loss (IOL) accounts for a sizable fraction of olfactory dysfunction, but very little is known about its etiology and electrophysiological changes in...
BACKGROUND
Idiopathic olfactory loss (IOL) accounts for a sizable fraction of olfactory dysfunction, but very little is known about its etiology and electrophysiological changes in the olfactory pathway.
METHODS
We analyzed the physiology of IOL using chemosensory event-related potentials (ERPs) (olfactory and trigeminal: oERP and tERP) and olfactory pathway magnetic resonance imaging (MRI) measured in adult patients with IOL and healthy controls. Subjective olfactory function was measured by Toyota and Takagi (T&T) olfactometry and Sniffin' Sticks (SS).
RESULTS
Olfactory function was worse in patients with IOL compared to controls (T&T, p < 0.001; SS, p < 0.001). oERPs could be evoked in 17 IOL patients. Signals in these patients showed lower amplitude in the N and P waves than controls (p < 0.05 for both), but there were no difference in latency between the 2 groups (p > 0.05). tERP were detected in all patients and controls; there were no differences in latency and nor amplitude between the 2 groups (p > 0.05). The olfactory bulb (OB) volume was significantly smaller in the IOL group than controls (p < 0.001), but there was no difference in the olfactory sulcus depth between groups (p > 0.05). Better olfactory function was associated with increasing magnitude of N amplitude in oERPs (p < 0.05) and increasing OB volume (p < 0.05).
CONCLUSION
IOL patients show neurophysiologic deficits and some anatomic differences compared to healthy controls.
Topics: Adult; Evoked Potentials; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Olfactory Bulb; Olfactory Pathways; Smell
PubMed: 29782071
DOI: 10.1002/alr.22144 -
Brain Structure & Function Nov 2017The nucleus of the lateral olfactory tract (nLOT) is a relatively small component of the cortical pallial amygdala, with peculiar neurogenic, neurochemical and...
The nucleus of the lateral olfactory tract (nLOT) is a relatively small component of the cortical pallial amygdala, with peculiar neurogenic, neurochemical and connectivity patterns. Although it has been suggested that it might be involved in non-pheromonal olfactory-guided behaviors, particularly feeding, the functional implications of the nLOT have never been investigated. In view of this fact, we have tackled this subject by performing a series of behavioral tests and by quantifying biological and biochemical parameters in sexually naïve adult male rats that were submitted to bilateral excitotoxic lesions of the nLOT. nLOT-lesioned rats had severe olfactory deficits with inability to detect and discriminate between odors. Additionally, they did not display innate behavioral responses to biologically relevant chemosignals. Specifically, nLOT-lesioned rats did not show avoidance towards predator odors or aggressive behaviors towards intruders, and had severely impaired sexual behavior. In fact, nLOT lesions abolished preference for odors of receptive females, reduced chemoinvestigatory behavior and eliminated mounting behavior. nLOT-lesioned rats had normal circulating levels of testosterone, did not display anxiety- or depressive-like behaviors, and had unimpaired cognitive functions and fear acquisition and memory. Altogether, our results suggest that the nLOT integrity is required for the normal functioning of the olfactory system.
Topics: Aggression; Animals; Anxiety; Avoidance Learning; Behavior, Animal; Depression; Discrimination, Psychological; Male; Odorants; Olfactory Bulb; Rats, Wistar; Sexual Behavior, Animal; Smell
PubMed: 28424894
DOI: 10.1007/s00429-017-1422-2 -
Molecules (Basel, Switzerland) Sep 2013In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis... (Review)
Review
In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis throughout adult life. Although mechanisms underlying adult neurogenesis have been largely investigated in animals, to some degree they remain unclear in humans. Based on human research findings, the present review will focus on the olfactory bulb as an evidence of the astonishing plasticity of the human olfactory system.
Topics: Animals; Humans; Neurogenesis; Neuronal Plasticity; Neurons; Olfactory Bulb; Olfactory Perception
PubMed: 24048289
DOI: 10.3390/molecules180911586