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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 -
PLoS Pathogens Jun 2022Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses...
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.
Topics: Animals; Betacoronavirus 1; COVID-19; Coronavirus Infections; Humans; Mice; Olfaction Disorders; SARS-CoV-2; Smell; Swine
PubMed: 35759516
DOI: 10.1371/journal.ppat.1010667 -
EBioMedicine Dec 2022Animal experiments have demonstrated the dependency of cerebrospinal fluid clearance function on age and sleep, which partially underlay the cognitive decline in the...
BACKGROUND
Animal experiments have demonstrated the dependency of cerebrospinal fluid clearance function on age and sleep, which partially underlay the cognitive decline in the elderly. However, human evidence is lacking, which could be mainly attributed to the limited methods of cerebrospinal fluid clearance function assessment.
METHOD
Serial T1-weighted and T2-fluid attenuated inversion recovery imaging were performed in 92 patients before and at multiple time points including 4.5 h, 15 h and 39 h after intrathecal injection of contrast agent to visualize the putative meningeal lymphatic pathway, peri-olfactory nerve pathway, and peri-optic nerve pathway. We defined the clearance function as the percentage change in signal unit ratio of critical locations in these pathways from baseline to 39 h after intrathecal injection, and further analysed their relationships with age, sleep, and cognitive function.
FINDINGS
Cerebrospinal fluid clearance through the putative meningeal lymphatic and perineural pathways were clearly visualized. The clearance function of putative meningeal lymphatic and perineural pathways were impaired with ageing (all P < 0.05). The clearance function through peri-olfactory nerve pathway in inferior turbinate was positively correlated with sleep quality and cognitive function (both P < 0.05), and mediated the association of sleep quality with cognitive function (percent change in β [bootstrap 95% CI]: 33% [-0.220, -0.007]).
INTERPRETATION
The impaired clearance through putative peri-olfactory nerve pathway may explain the cognitive decline in patients with sleep disturbance. The study shows a promising method to assess cerebrospinal fluid clearance function of putative peri-neural pathways via dynamic magnetic resonance imaging with intrathecal injection of contrast agent.
FUNDING
This work was supported by the National Natural Science Foundation of China (81971101, 82171276 and 82101365).
Topics: Animals; Humans; Aged; Contrast Media; Cognitive Dysfunction; Aging; Magnetic Resonance Imaging; Dyssomnias
PubMed: 36442319
DOI: 10.1016/j.ebiom.2022.104381 -
Sensors (Basel, Switzerland) Jan 2023A new hypothesis for the mechanism of olfaction is presented. It begins with an odorant molecule binding to an olfactory receptor. This is followed by the quantum...
A new hypothesis for the mechanism of olfaction is presented. It begins with an odorant molecule binding to an olfactory receptor. This is followed by the quantum biology event of inelastic electron tunneling as has been suggested with both the vibration and swipe card theories. It is novel in that it is not concerned with the possible effects of the tunneled electrons as has been discussed with the previous theories. Instead, the high energy state of the odorant molecule in the receptor following inelastic electron tunneling is considered. The hypothesis is that, as the high energy state decays, there is fluorescence luminescence with radiative emission of multiple photons. These photons pass through the supporting sustentacular cells and activate a set of olfactory neurons in near-simultaneous timing, which provides the temporal basis for the brain to interpret the required complex combinatorial coding as an odor. The Luminescence Hypothesis of Olfaction is the first to present the necessity of or mechanism for a 1:3 correspondence of odorant molecule to olfactory nerve activations. The mechanism provides for a consistent and reproducible time-based activation of sets of olfactory nerves correlated to an odor. The hypothesis has a biological precedent: an energy feasibility assessment is included, explaining the anosmia seen with COVID-19, and can be confirmed with existing laboratory techniques.
Topics: Humans; Smell; Luminescence; COVID-19; Olfactory Receptor Neurons; Odorants; Receptors, Odorant
PubMed: 36772376
DOI: 10.3390/s23031333 -
Current Drug Delivery Nov 2012The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine... (Review)
Review
The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive route for drug administration. The blood flow into the nasal region is slightly more than reabsorbed back into the nasal veins, but the excess will drain into the lymph vessels, making this region a very attractive route for vaccine delivery. Many of the side effects seen following intranasal administration are caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial nerve (trigeminus nerve) is responsible for sensing pain and irritation following nasal administration but the 7th cranial nerve (facial nerve) will respond to such irritation by stimulating glands and cause facial expressions in the subject. The first cranial nerve (olfactory nerve), however, is the target when direct absorption into the brain is the goal, since this is the only site in our body where the central nervous system is directly expressed on the mucosal surface. The nasal mucosa contains 7 cell types and 4 types of glands. Four types of cells and 2 types of glands are located in the respiratory region but 6 cell types and 2 types of glands are found in the olfactory region.
Topics: Administration, Intranasal; Animals; Humans; Nasal Cavity; Nasal Mucosa; Pharmaceutical Preparations; Vaccines
PubMed: 22788696
DOI: 10.2174/156720112803529828 -
Neurotoxicity Research Jun 2020As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the... (Review)
Review
As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Cerebrovascular Disorders; Combined Modality Therapy; Consciousness Disorders; Coronavirus Infections; Dizziness; Encephalitis, Viral; Endothelial Cells; Fatigue; Headache; Humans; Intracranial Hypertension; Mental Disorders; Mood Disorders; Nervous System Diseases; Neurons; Olfactory Nerve; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Prevalence; Prognosis; Psychotherapy; Psychotropic Drugs; Receptors, Virus; Retrospective Studies; SARS-CoV-2; Sensation Disorders; Spike Glycoprotein, Coronavirus
PubMed: 32399719
DOI: 10.1007/s12640-020-00219-8 -
Frontiers in Cell and Developmental... 2021The central nervous system (CNS) has very limited capacity to regenerate after traumatic injury or disease. In contrast, the peripheral nervous system (PNS) has far... (Review)
Review
The central nervous system (CNS) has very limited capacity to regenerate after traumatic injury or disease. In contrast, the peripheral nervous system (PNS) has far greater capacity for regeneration. This difference can be partly attributed to variances in glial-mediated functions, such as axon guidance, structural support, secretion of growth factors and phagocytic activity. Due to their growth-promoting characteristic, transplantation of PNS glia has been trialed for neural repair. After peripheral nerve injuries, Schwann cells (SCs, the main PNS glia) phagocytose myelin debris and attract macrophages to the injury site to aid in debris clearance. One peripheral nerve, the olfactory nerve, is unique in that it continuously regenerates throughout life. The olfactory nerve glia, olfactory ensheathing cells (OECs), are the primary phagocytes within this nerve, continuously clearing axonal debris arising from the normal regeneration of the nerve and after injury. In contrast to SCs, OECs do not appear to attract macrophages. SCs and OECs also respond to and phagocytose bacteria, a function likely critical for tackling microbial invasion of the CNS via peripheral nerves. However, phagocytosis is not always effective; inflammation, aging and/or genetic factors may contribute to compromised phagocytic activity. Here, we highlight the diverse roles of SCs and OECs with the focus on their phagocytic activity under physiological and pathological conditions. We also explore why understanding the contribution of peripheral glia phagocytosis may provide us with translational strategies for achieving axonal regeneration of the injured nervous system and potentially for the treatment of certain neurological diseases.
PubMed: 33898462
DOI: 10.3389/fcell.2021.660259 -
BioMed Research International 2016. Objective electrophysiological methods for investigations of the organ of smell consist in recordings of olfactory cortex responses to specific, time restricted odor...
. Objective electrophysiological methods for investigations of the organ of smell consist in recordings of olfactory cortex responses to specific, time restricted odor stimuli. In hypothyroidism have impaired sense of smell. . Two groups: control of 31 healthy subjects and study group of 21 with hypothyroidism. The inclusion criterion for the study group was the TSH range from 3.54 to 110 IU/mL. . Assessment of the latency time of evoked responses from the olfactory nerve N1 and the trigeminal nerve N5 using two smells of mint and anise in hypothyroidism. . The smell perception in subjective olfactory tests was normal in 85% of the hypothyroid group. Differences were noticed in the objective tests. The detailed intergroup analysis of latency times of recorded cortical responses and performed by means between the groups of patients with overt clinical hypothyroidism versus subclinical hypothyroidism demonstrated a significant difference ( < 0.05) whereas no such differences were found between the control group versus subclinical hypothyroidism group ( > 0.05). . We can conclude that registration of cortex potentials at irritation of olfactory and trigeminal nerves offers possibilities for using this method as an objective indicator of hypothyroidism severity and prognostic process factor.
PubMed: 27656655
DOI: 10.1155/2016/9583495 -
Anatomical Record (Hoboken, N.J. : 2007) Oct 2018The nasal cavity performs several crucial functions in mammals, including rodents, being involved in respiration, behavior, reproduction, and olfaction. Its anatomical... (Review)
Review
The nasal cavity performs several crucial functions in mammals, including rodents, being involved in respiration, behavior, reproduction, and olfaction. Its anatomical structure is complex and divided into several regions, including the olfactory recess where the olfactory mucosa (OM) is located and where the capture and interaction with the environmental odorants occurs. Among the cells of this region are the OM mesenchymal stem cells (MSCs), whose location raises the possibility that these cells could be involved in the peculiar ability of the olfactory nerve to regenerate continuously throughout life, although this relationship has not yet been confirmed. These cells, like all MSCs, present functional characteristics that make them candidates in new therapies associated with regenerative medicine, namely to promote the regeneration of the peripheral nerve after injury. The availability of stem cells to be therapeutically applied essentially depends on their collection in the tissue of origin. In the case of mice and rat's OM-MSCs, knowledge about the anatomy and histology of their nasal cavity is essential in establishing effective collection protocols. The present article describes the morphological characteristics of rodent's OM and establishes an alternative protocol for access to the olfactory recess and collection of the OM. Anat Rec, 301:1678-1689, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Animals; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Nasal Cavity; Olfactory Mucosa; Peripheral Nerve Injuries; Rats
PubMed: 29710430
DOI: 10.1002/ar.23844 -
Anatomical Record (Hoboken, N.J. : 2007) Feb 2023Cell migration from the olfactory placode (OP) is a well-known phenomenon wherein various cell types, such as gonadotropin-releasing hormone (GnRH)-producing neurons,...
Cell migration from the olfactory placode (OP) is a well-known phenomenon wherein various cell types, such as gonadotropin-releasing hormone (GnRH)-producing neurons, migrate toward the telencephalon (TEL) during early embryonic development. However, the spatial relationship between early migratory cells and the forebrain is unclear. We examined the early development of whole-mount chick embryos to observe the three-dimensional spatial relationship among OP-derived migratory neurons, olfactory nerve (ON), and TEL. Migratory neurons that express highly polysialylated neural cell adhesion molecule (PSA-NCAM) emerge from the OP and spread over a relatively wide TEL area at the Hamburger and Hamilton (HH) stage 17. Most migratory neurons form a cellular cord between the olfactory pit and rostral TEL within HH18-20. The earliest axons from the olfactory epithelium (OE) were detected along this neuronal cord using DiI-labeling at HH21. Furthermore, a few PSA-NCAM-positive neurons were dispersed around the cellular cord and over the lateral TEL at HH18. A long cellular cord branch extending to the lateral TEL was transiently observed within HH18-24. These results suggest a novel migratory route of OP-derived neurons during the early developmental stages. Following GFP vector introduction into the OP of HH13-15 embryos, labeled neurons were detected around and within the lateral TEL at HH23 and HH27. At HH36, labeled cells were observed in the rostral-lateral TEL, including the olfactory bulb (OB) region. GFP-labeled and calretinin-positive neurons were detected in the OB, suggesting that early OP-derived neurons enter the forebrain and function as interneurons in the OB.
Topics: Animals; Chick Embryo; Axons; Cell Movement; Neurons; Olfactory Bulb; Olfactory Nerve; Prosencephalon; Telencephalon
PubMed: 36104941
DOI: 10.1002/ar.25080