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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 -
International Journal of Molecular... Mar 2024There is very little knowledge regarding the terminal nerve, from its implications in the involvement and pathogenesis of certain conditions, to its embryological... (Review)
Review
There is very little knowledge regarding the terminal nerve, from its implications in the involvement and pathogenesis of certain conditions, to its embryological origin. With this review, we try to summarize the most important evidence on the terminal nerve, aiming to clarify its anatomy and the various functions attributed to it, to better interpret its potential involvement in pathological processes. Recent studies have also suggested its potential role in the control of human reproductive functions and behaviors. It has been hypothesized that it plays a role in the unconscious perception of specific odors that influence autonomic and reproductive hormonal systems through the hypothalamic-pituitary-gonadal axis. We used the PubMed database and found different articles which were then selected independently by three authors. We found 166 articles, of which, after careful selection, only 21 were analyzed. The terminal nerve was always thought to be unimportant in our body. It was well studied in different types of animals, but few studies have been completed in humans. For this reason, its function remains unknown. Studies suggest a possible implication in olfaction due to the anatomical proximity with the olfactive nerve. Others suggest a more important role in reproduction and sexual behaviors. New emerging information suggests a possible role in Kallmann syndrome and COVID-19.
Topics: Animals; Humans; Smell; Kallmann Syndrome; Nerve Endings; Autonomic Nervous System; COVID-19
PubMed: 38612730
DOI: 10.3390/ijms25073920 -
ORL; Journal For Oto-rhino-laryngology... 2024Zinc deficiency may worsen the severity of olfactory dysfunction; however, the relationship between serum zinc levels and therapeutic effects on olfactory dysfunction...
INTRODUCTION
Zinc deficiency may worsen the severity of olfactory dysfunction; however, the relationship between serum zinc levels and therapeutic effects on olfactory dysfunction remains uncertain. This study investigated the relationship between normalising serum zinc levels and the therapeutic effects on olfactory dysfunction.
METHODS
Forty-two patients diagnosed with post-infectious, post-traumatic, and idiopathic olfactory dysfunction, with serum zinc levels <70 μg/dL, were included in the study. All patients were treated with mecobalamin, tokishakuyakusan, and polaprezinc. The patients were divided into 2 groups: the zinc-normalised (≥70 μg/dL) and zinc-deficient (<70 μg/dL) groups, based on their post-treatment serum zinc levels. Olfactory test results were compared in each of the 2 groups.
RESULTS
The patients were treated for a median of 133 days. The zinc-normalised group had significantly better results in all olfactory tests (detection/recognition thresholds of the T&T olfactometer, odour identification test (Open Essence), Visual Analogue Scale for olfactory dysfunction, and self-administered odour questionnaire). In contrast, only the self-administered odour questionnaire showed a significant improvement in the zinc-deficient group, with no significant differences observed in the other olfactory tests. When comparing the changes in the olfactory test scores between the 2 groups, significant differences were observed in the detection/recognition thresholds of the T&T olfactometer test and Open Essence results.
CONCLUSION
These findings suggest that patients with olfactory dysfunction may have difficulty improving their olfactory function if they also have zinc deficiency. Furthermore, normalisation of zinc deficiency may contribute to the improvement of olfactory dysfunction with general treatment.
Topics: Humans; Zinc; Olfaction Disorders; Female; Male; Middle Aged; Adult; Carnosine; Aged; Vitamin B 12; Organometallic Compounds; Treatment Outcome; Zinc Compounds; Smell
PubMed: 38565084
DOI: 10.1159/000538594 -
Journal of Neurosurgery Apr 2024The authors aimed to review the frontal lobe's surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results.
OBJECTIVE
The authors aimed to review the frontal lobe's surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results.
METHODS
Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis.
RESULTS
Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months.
CONCLUSIONS
Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.
Topics: Humans; Brain Neoplasms; Retrospective Studies; Glioma; Neurosurgical Procedures; Craniotomy
PubMed: 38564815
DOI: 10.3171/2023.7.JNS231363 -
Anatomia, Histologia, Embryologia May 2024The ultrastructure of the olfactory system of most fossorial rodents remains largely unexplored. This study sought to investigate the functional structure of the...
The ultrastructure of the olfactory system of most fossorial rodents remains largely unexplored. This study sought to investigate the functional structure of the olfactory mucosa and olfactory bulb of two species of fossorial rodents that have distinct behaviour and ecology, the East African root rat (RR) and the naked mole rat (NMR). Transmission electron microscopy and scanning electron microscopy were employed. The basic ultrastructural design of the olfactory system of the two species was largely comparable. In both species, the olfactory mucosa comprised an olfactory epithelium and an underlying lamina propria. The olfactory epithelium revealed olfactory knobs, cilia and microvilli apically and sustentancular cells, olfactory receptor neurons and basal cells in the upper, middle and basal zones, respectively. The lamina propria was constituted by Bowman's glands, olfactory nerve bundles and vasculature supported by loose connective tissue. Within the olfactory bulb, intracellular and extracellular structures including cell organelles, axons and dendrites were elucidated. Notable species differences were observed in the basal zone of the olfactory epithelium and on the luminal surface of the olfactory mucosa. The basal zone of the olfactory epithelium of the RR consisted of a single layer of flattened electron-dense horizontal basal cells while the NMR had juxtaposed electron-dense and electron-lucent heterogenous cells, an occurrence seen as being indicative of quiescent and highly proliferative states of the olfactory epithelia in the two species, respectively. The olfactory epithelial surface of the NMR comprised an elaborate cilia network that intertwined extensively forming loop-like structures whereas in the RR, the surface was rugged and consisted of finger-like processes and irregular masses. With gross and histological studies showing significant differences in the olfactory structures of the two species, these findings are a further manifestation that the olfactory system of the RR and the NMR have evolved differently to reflect their varied olfactory functional needs.
Topics: Animals; Axons; Cilia; Mole Rats; Olfactory Receptor Neurons; Africa, Eastern
PubMed: 38563613
DOI: 10.1111/ahe.13034 -
The Journal of Neuroscience : the... May 2024Creating and evaluating predictions are considered important features in sensory perception. Little is known about processing differences between the senses and their...
Creating and evaluating predictions are considered important features in sensory perception. Little is known about processing differences between the senses and their cortical substrates. Here, we tested the hypothesis that olfaction, the sense of smell, would be highly dependent on (nonolfactory) object-predictive cues and involve distinct cortical processing features. We developed a novel paradigm to compare prediction error processing across senses. Participants listened to spoken word cues (e.g., "lilac") and determined whether target stimuli (odors or pictures) matched the word cue or not. In two behavioral experiments (total = 113; 72 female), the disparity between congruent and incongruent response times was exaggerated for olfactory relative to visual targets, indicating a greater dependency on predictive verbal cues to process olfactory targets. A preregistered fMRI study ( = 30; 19 female) revealed the anterior cingulate cortex (a region central for error detection) being more activated by incongruent olfactory targets, indicating a role for olfactory predictive error processing. Additionally, both the primary olfactory and visual cortices were significantly activated for incongruent olfactory targets, suggesting olfactory prediction errors are dependent on cross-sensory processing resources, whereas visual prediction errors are not. We propose that olfaction is characterized by a strong dependency on predictive (nonolfactory) cues and that odors are evaluated in the context of such predictions by a designated transmodal cortical network. Our results indicate differences in how predictive cues are used by different senses in rapid decision-making.
Topics: Humans; Female; Male; Adult; Magnetic Resonance Imaging; Olfactory Perception; Young Adult; Cues; Smell; Nerve Net; Odorants; Brain Mapping; Adolescent; Reaction Time; Cerebral Cortex; Photic Stimulation
PubMed: 38561229
DOI: 10.1523/JNEUROSCI.1232-23.2024 -
Otolaryngology--head and Neck Surgery :... Jul 2024
Topics: Humans; Autonomic Nerve Block; COVID-19; Olfaction Disorders; SARS-CoV-2; Stellate Ganglion
PubMed: 38558456
DOI: 10.1002/ohn.740 -
Auris, Nasus, Larynx Jun 2024Periglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone,...
OBJECTIVE
Periglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone, migrate to the olfactory bulb via the Rostral Migratory Stream (RMS), and differentiate into mature cells within the olfactory bulb throughout postnatal life. While the regulation of neuroblast development is known to be affected by external stimuli, there is a lack of information concerning changes that occur during the recovery process after injury caused by external stimuli. To address this gap in research, the present study conducted histological observations to investigate changes in the olfactory bulb and RMS occurring after the degeneration and regeneration of olfactory neurons.
METHODS
To create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test.
RESULTS
Olfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days.
CONCLUSION
These results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input.
Topics: Animals; Olfactory Bulb; Methimazole; Mice; Cell Movement; Antithyroid Agents; Olfactory Nerve; Olfactory Marker Protein; Disease Models, Animal; Male
PubMed: 38522356
DOI: 10.1016/j.anl.2024.01.009 -
Neuroscience Letters Mar 2024Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the...
Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the cranial nerves that have a role in the transport of brain lymphatics vessels (LVs), their localization, diameter, and number using podoplanin (PDPN) and CD31 immunohistochemistry (IHC) and Western blotting. Cranial nerve samples from 6 human cases (3 cadavers, and 3 autopsies) were evaluated for IHC and 3 autopsies for Western blotting. The IHC staining showed LVs along the optic, olfactory, oculomotor, trigeminal, facial, glossopharyngeal, accessory, and vagus nerves. However, no LVs present along the trochlear, abducens, vestibulocochlear, and hypoglossal nerves. The LVs were predominantly localized at the endoneurium of the cranial nerve that has motor components, and LVs in the cranial nerves that had sensory components were present in all 3 layers. The number of LVs accompanying the olfactory, optic, and trigeminal nerves was classified as numerous; oculomotor, glossopharyngeal, vagus, and accessory was moderate; and facial nerves was few. The largest diameter of LVs was in the epineurium and the smallest one was in the endoneurium. The majority of Western blotting results correlated with the IHC. The present findings suggest that specific cranial nerves with variable quantities provide a pathway for the transport of wastes from the brain to dCLN. Thus, the knowledge of the transport of brain lymphatics along cranial nerves may help understand the pathophysiology of various neurological diseases.
Topics: Humans; Cranial Nerves; Brain; Vagus Nerve; Facial Nerve; Skull; Trigeminal Nerve; Hypoglossal Nerve; Glossopharyngeal Nerve; Oculomotor Nerve; Abducens Nerve
PubMed: 38519013
DOI: 10.1016/j.neulet.2024.137737 -
Journal of Chemical Neuroanatomy Apr 2024Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients'... (Review)
Review
Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients' quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.
Topics: Humans; Chronic Pain; Animals; Olfactory Bulb; Neuroglia; Cell Transplantation
PubMed: 38492895
DOI: 10.1016/j.jchemneu.2024.102413