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The European Journal of Neuroscience May 2024Across vertebrate species, the olfactory epithelium (OE) exhibits the uncommon feature of lifelong neuronal turnover. Epithelial stem cells give rise to new neurons that...
Across vertebrate species, the olfactory epithelium (OE) exhibits the uncommon feature of lifelong neuronal turnover. Epithelial stem cells give rise to new neurons that can adequately replace dying olfactory receptor neurons (ORNs) during developmental and adult phases and after lesions. To relay olfactory information from the environment to the brain, the axons of the renewed ORNs must reconnect with the olfactory bulb (OB). In Xenopus laevis larvae, we have previously shown that this process occurs between 3 and 7 weeks after olfactory nerve (ON) transection. In the present study, we show that after 7 weeks of recovery from ON transection, two functionally and spatially distinct glomerular clusters are reformed in the OB, akin to those found in non-transected larvae. We also show that the same odourant response tuning profiles observed in the OB of non-transected larvae are again present after 7 weeks of recovery. Next, we show that characteristic odour-guided behaviour disappears after ON transection but recovers after 7-9 weeks of recovery. Together, our findings demonstrate that the olfactory system of larval X. laevis regenerates with high accuracy after ON transection, leading to the recovery of odour-guided behaviour.
PubMed: 38758670
DOI: 10.1111/ejn.16375 -
Frontiers in Neurology 2024Long COVID, also known as Post-COVID-19 syndrome, is characterized by multisystemic symptoms that persists for weeks to years beyond acute infection. It...
BACKGROUND
Long COVID, also known as Post-COVID-19 syndrome, is characterized by multisystemic symptoms that persists for weeks to years beyond acute infection. It disproportionately affects women and those with pre-existing anxiety/depression, conditions more prevalent in females. The vagus nerve, with its extensive innervation and regulation of critical bodily functions, has become a focal point for therapeutic interventions. Transcutaneous vagus nerve stimulation (t-VNS) has emerged as a promising non-invasive treatment for COVID-19 conditions.
METHODS
This pilot study assessed the efficacy of t-VNS in 24 female Long COVID patients (45.8 ± 11.7 years old; 20.2 ± 7.1 months since infection), who underwent a 10-day t-VNS intervention at home (30 min/session, twice a day). Cognition was considered the primary outcome, with anxiety, depression, sleep, fatigue, and smell as secondary outcomes. Outcomes were measured at baseline, post-intervention, and 1-month follow-up.
RESULTS
Significant improvements were observed in various cognitive functions, anxiety, depression, and sleep at post-intervention, with benefits remaining or progressing at 1-month follow-up. Improvements in fatigue were delayed, reaching statistical significance at 1-month follow-up compared to baseline. No significant changes were noted in olfactory performance.
CONCLUSION
This pilot study provides preliminary evidence supporting the potential of t-VNS as a therapeutic intervention for female Long COVID patients. The encouraging results justify further rigorous investigation through larger, randomized controlled trials to confirm the efficacy of t-VNS, assess its generalizability to male cohorts, and explore biological markers to inform personalized treatment approaches. Our findings support the allocation of resources to conduct such trials and advance the understanding of t-VNS as a potential treatment for Long COVID.
PubMed: 38756213
DOI: 10.3389/fneur.2024.1393371 -
Proceedings of the National Academy of... May 2024The mammalian brain implements sophisticated sensory processing algorithms along multilayered ("deep") neural networks. Strategies that insects use to meet similar...
The mammalian brain implements sophisticated sensory processing algorithms along multilayered ("deep") neural networks. Strategies that insects use to meet similar computational demands, while relying on smaller nervous systems with shallow architectures, remain elusive. Using as a model, we uncover the algorithmic role of odor preprocessing by a shallow network of compartmentalized olfactory receptor neurons. Each compartment operates as a ratiometric unit for specific odor-mixtures. This computation arises from a simple mechanism: electrical coupling between two differently sized neurons. We demonstrate that downstream synaptic connectivity is shaped to optimally leverage amplification of a hedonic value signal in the periphery. Furthermore, peripheral preprocessing is shown to markedly improve novel odor classification in a higher brain center. Together, our work highlights a far-reaching functional role of the sensory periphery for downstream processing. By elucidating the implementation of powerful computations by a shallow network, we provide insights into general principles of efficient sensory processing algorithms.
Topics: Animals; Odorants; Olfactory Receptor Neurons; Smell; Drosophila melanogaster; Algorithms; Drosophila; Olfactory Pathways; Models, Neurological; Nerve Net
PubMed: 38753511
DOI: 10.1073/pnas.2316799121 -
Experimental Brain Research Jul 2024In the human brain, the regions responsible for emotion processing, motivation, and memory are heavily influenced by olfaction, whose neural pathway is directly exposed...
In the human brain, the regions responsible for emotion processing, motivation, and memory are heavily influenced by olfaction, whose neural pathway is directly exposed to the outer world. In this study, we used fMRI to examine how different olfactory conditions might affect the functional connectivity circuit underlying working memory in the brain. To this end, 30 adults (aged 20-35), 13 males and 17 females, with high educational levels were chosen. Participants were screened for potential olfactory issues before undergoing the Sniffin' sticks test, which was part of the inclusion criteria. Before imaging, each participant was given the required level of training and was then asked to complete four olfactory tests involving pleasant and unpleasant odors, air, and null stimulation. The results of Seed-based analysis suggested a function connection between the inferior parietal region and the left frontal pole region upon olfactory stimulation with vanilla scent in contrast to null stimulation in this comparison, ROI-based analysis revealed an inverse synchronous among the entorhinal cortex, orbitofrontal cortex, and dorsolateral prefrontal cortex (dlPFC). Both dlPFC and hippocampus were involved in olfactory discrimination between two different stimulants. Our findings indicate the presence of inverse correlations between several regions associated with olfaction and working memory, with pleasant scents leaving a stronger impact on the working memory-related areas, particularly the inferior parietal region.
Topics: Humans; Male; Female; Adult; Memory, Short-Term; Magnetic Resonance Imaging; Young Adult; Olfactory Perception; Odorants; Brain Mapping; Nerve Net; Brain; Smell; Neural Pathways
PubMed: 38753044
DOI: 10.1007/s00221-024-06848-1 -
Cell Reports May 2024
PubMed: 38728137
DOI: 10.1016/j.celrep.2024.113890 -
Proceedings of the National Academy of... May 2024During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical...
During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Sonic Hedgehog (Shh) signaling promotes the cortical RGC lineage switch to generate cortical oligodendrocytes and OB interneurons. During this process, cortical RGCs generate intermediate progenitor cells that express critical gliogenesis genes , and . The increased expression and appearance of Egfr and Olig2 cortical progenitors are concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Furthermore, the transcriptional regulation of and has not been explored. Here, we show that in cortical progenitor cells, multiple regulatory programs, including Pax6 and Gli3, prevent precocious expression of , a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple enhancers that control expression in cortical progenitors and show that the mechanisms for regulating expression are conserved between the mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
Topics: Animals; Neurogenesis; Cerebral Cortex; Basic Helix-Loop-Helix Transcription Factors; ErbB Receptors; Mice; Oligodendrocyte Transcription Factor 2; Nerve Tissue Proteins; Hedgehog Proteins; PAX6 Transcription Factor; Neural Stem Cells; Homeodomain Proteins; Zinc Finger Protein Gli3; Eye Proteins; Repressor Proteins; Paired Box Transcription Factors; Neuroglia; Gene Expression Regulation, Developmental; Signal Transduction; Olfactory Bulb; Cell Lineage; Humans
PubMed: 38713624
DOI: 10.1073/pnas.2321711121 -
Heliyon May 2024Chemosensation is important for the survival and reproduction of animals. The odorant binding proteins (OBPs) are thought to be involved in chemosensation together with...
Chemosensation is important for the survival and reproduction of animals. The odorant binding proteins (OBPs) are thought to be involved in chemosensation together with chemosensory receptors. While OBPs were initially considered to deliver hydrophobic odorants to olfactory receptors in the aqueous lymph solution, recent studies suggest more complex roles in various organs. Here, we use transgenes to systematically analyze the expression patterns of all 52 members of the gene family and 3 related chemosensory protein genes in adult , focusing on chemosensory organs such as the antenna, maxillary palp, pharynx, and labellum, and other organs such as the brain, ventral nerve cord, leg, wing, and intestine. The OBPs were observed to express in diverse organs and in multiple cell types, suggesting that these proteins can indeed carry out diverse functional roles. Also, we constructed 10 labellar-expressing mutants, and obtained behavioral evidence that these OBPs may be involved in bitter sensing. The resources we constructed should be useful for future OBP gene family research.
PubMed: 38694054
DOI: 10.1016/j.heliyon.2024.e29358 -
ACS Sensors May 2024Artificial olfactory synaptic devices with low energy consumption and low detection limits are important for the further development of neuromorphic computing and...
Artificial olfactory synaptic devices with low energy consumption and low detection limits are important for the further development of neuromorphic computing and intelligent robotics. In this work, an ultralow energy consumption and low detection limit imitation olfactory synaptic device based on organic field-effect transistors (OFETs) was prepared. The aggregation state of poly(diketopyrrolopyrrole-selenophene) (PTDPP) semiconductor films is modulated by adding unfavorable solvents and annealing treatments to obtain excellent charge transfer and gas synaptic properties. The regulated OFET device can execute basic biological synaptic functions, including excitatory postsynaptic currents (EPSCs), paired-pulse facilitation (PPF), and the transition from short-term to long-term plasticity, at an ultralow operating voltage of -0.0005 V. The ultralow energy consumption during the biomimetic simulation is in the range of 8.94-88 fJ per spike. Noteworthily, the gas detection limit of the device is as low as 50 ppb, well below normal human NO gas perception limits (100-1000 ppb). Additionally, high-pass filtering, Pavlovian conditioned reflexes, and decoding of "Morse code" were simulated. Finally, a grid-free conformal device with outstanding flexibility and stability was fabricated. In conclusion, the control of semiconductor thin-film aggregation provides effective guidance for preparing low-energy-consumption, highly sensitive olfactory nerve-mimicking devices and promoting the development of wearable electronics.
Topics: Transistors, Electronic; Semiconductors; Biomimetics; Humans; Biomimetic Materials; Limit of Detection; Synapses
PubMed: 38688032
DOI: 10.1021/acssensors.4c00616 -
The FEBS Journal May 2024Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a transmembrane protein that, when cleaved by metalloproteases through a process called ectodomain...
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a transmembrane protein that, when cleaved by metalloproteases through a process called ectodomain shedding, binds to the EGF receptor (EGFR), activating downstream signaling. The HB-EGF/EGFR pathway is crucial in development and is involved in numerous pathophysiological processes. In this issue of The FEBS Journal, Sireci et al. reveal a previously unexplored function of the HB-EGF/EGFR pathway in promoting neuronal progenitor proliferation and sensory neuron regeneration in the zebrafish olfactory epithelium in response to injury.
Topics: Heparin-binding EGF-like Growth Factor; Animals; ErbB Receptors; Signal Transduction; Zebrafish; Humans; Cell Proliferation; Neurons; Nerve Regeneration; Olfactory Mucosa
PubMed: 38680125
DOI: 10.1111/febs.17143 -
International Journal of Molecular... Apr 2024The primary entry point of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the nasal mucosa, where viral-induced inflammation occurs. When the immune...
The primary entry point of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the nasal mucosa, where viral-induced inflammation occurs. When the immune response fails against SARS-CoV-2, understanding the altered response becomes crucial. This study aimed to compare SARS-CoV-2 immunological responses in the olfactory and respiratory mucosa by focusing on epithelia and nerves. Between 2020 and 2022, we obtained post mortem tissues from the olfactory cleft from 10 patients with histologically intact olfactory epithelia (OE) who died with or from COVID-19, along with four age-matched controls. These tissues were subjected to immunohistochemical reactions using antibodies against T cell antigens CD3, CD8, CD68, and SARS spike protein for viral evidence. Deceased patients with COVID-19 exhibited peripheral lymphopenia accompanied by a local decrease in CD3 cells in the OE. However, SARS-CoV-2 spike protein was sparsely detectable in the OE. With regard to the involvement of nerve fibers, the present analysis suggested that SARS-CoV-2 did not significantly alter the immune response in olfactory or trigeminal fibers. On the other hand, SARS spike protein was detectable in both nerves. In summary, the post mortem investigation demonstrated a decreased T cell response in patients with COVID-19 and signs of SARS-CoV-2 presence in olfactory and trigeminal fibers.
Topics: Humans; COVID-19; Male; Female; SARS-CoV-2; Aged; Middle Aged; Nasal Mucosa; T-Lymphocytes; Aged, 80 and over; Spike Glycoprotein, Coronavirus; Olfactory Mucosa; Adult; Autopsy
PubMed: 38674011
DOI: 10.3390/ijms25084427