-
Nature Communications Jun 2024Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors,...
Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors, as well as meningiomas and ependymomas. Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify ACSL3 and G6PD as two synthetic-lethal partners for NF2, both involved in lipid biogenesis and cellular redox. We find that NF2 mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as ME1. Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for G6PD is tolerated in the human population, G6PD could be a good pharmacological target for NFII.
Topics: Schwann Cells; Humans; CRISPR-Cas Systems; Glucosephosphate Dehydrogenase; Neurofibromin 2; Coenzyme A Ligases; Synthetic Lethal Mutations; Animals; Neurofibromatosis 2; NADP; Mice; Oxidation-Reduction
PubMed: 38879607
DOI: 10.1038/s41467-024-49298-7 -
The Journal of Biological Chemistry Jun 2024Glucoselysine (GL) is a unique advanced glycation end-product derived from fructose. The main source of fructose in vivo is the polyol pathway, and an increase in its...
Glucoselysine (GL) is a unique advanced glycation end-product derived from fructose. The main source of fructose in vivo is the polyol pathway, and an increase in its activity leads to diabetic complications. Here, we aimed to demonstrate that GL can serve as an indicator of the polyol pathway activity. Additionally, we propose a novel approach for detecting GL in peripheral blood samples using LC-MS/MS and evaluate its clinical usefulness. We successfully circumvent interference from fructoselysine, which shares the same molecular weight as GL, by performing ultrafiltration and hydrolysis without reduction, successfully generating adequate peaks for quantification in serum. Furthermore, using immortalized aldose reductase knockout mouse Schwann cells, we demonstrate that GL reflects the downstream activity of the polyol pathway and that GL produced intracellularly is released into the extracellular space. Clinical studies reveal that GL levels in patients with type 2 diabetes are significantly higher than those in healthy participants, while N-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1) levels are significantly lower. Both GL and MG-H1 show higher values among patients with vascular complications; however, GL varies more markedly than MG-H1 as well as hemoglobin A1c, fasting plasma glucose, and estimated glomerular filtration rate. Furthermore, GL remains consistently stable under various existing drug treatments for type 2 diabetes, whereas MG-H1 is impacted. To the best of our knowledge, we provide important insights in predicting diabetic complications caused by enhanced polyol pathway activity via assessment of GL levels in peripheral blood samples from patients.
PubMed: 38879006
DOI: 10.1016/j.jbc.2024.107479 -
Frontiers in Oncology 2024Schwannomas are benign, slow-growing tumors originating from the Schwann cells of nerve sheaths. Extracranial schwannomas are rare, particularly in pediatric...
Schwannomas are benign, slow-growing tumors originating from the Schwann cells of nerve sheaths. Extracranial schwannomas are rare, particularly in pediatric populations. Here, we report the case of a hypoglossal schwannoma in a 15-year-old male who experienced tongue paresthesia and fasciculations and difficulty swallowing two years before hospital admission. Magnetic resonance imaging showed an oval mass with sharp and regular limits of approximately 45 × 29 × 25 mm in the cranial portion of the right carotid adipose space, caudal to the right carotid and lateral foramen. The patient underwent surgery, and a histological examination confirmed a schwannoma of the hypoglossal nerve. Six months after surgery, the patient was symptom-free. The literature on schwannomas of the hypoglossal nerve is scarce, with only a few previously reported cases in the adult population. Despite their rarity, schwannomas should be considered in the differential diagnosis of masses located in the neck that present with lingual and occasionally auditory symptoms, even in pediatric patients. Surgical resection is recommended and has a low risk of long-term recurrence.
PubMed: 38863642
DOI: 10.3389/fonc.2024.1400335 -
Cureus May 2024Cutaneous granular cell tumors (GCTs) are rare tumors that typically exhibit benign clinical behavior and are likely of Schwann cell origin. Some histologic and...
Cutaneous granular cell tumors (GCTs) are rare tumors that typically exhibit benign clinical behavior and are likely of Schwann cell origin. Some histologic and immunohistochemical variants of GCTs may present challenges due to infiltrative growth patterns, perineural invasion, and expression of Melan-A. In this case report, we present a 27-year-old male who had previously been diagnosed with a typical GCT on the back a few years ago. The current biopsy from the proximal palm demonstrated a cytologically similar tumor with extensive perineural spread and notable positivity for Melan-A. Although uncommon, these features are consistent with the histological appearances of GCTs. The current views on the histogenesis of GCTs, clinical associations, differential diagnosis with melanoma, and histological criteria for malignant GCTs are discussed. A panel of immunohistochemical stains, including Inhibin-α and preferentially expressed antigen in melanoma (PRAME), is proposed for use in rare instances of Melan-A-positive GCTs.
PubMed: 38854338
DOI: 10.7759/cureus.59903 -
Brain and Behavior Jun 2024In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to...
INTRODUCTION
In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to other morphological indices commonly employed in studies of autism spectrum disorder (ASD). The current study sought to determine if intracortical myelin content (MC) and its age-related trajectories differ between middle aged to older adults with ASD and age-matched typical comparison participants.
METHODS
Data from 30 individuals with ASD and 36 age-matched typical comparison participants aged 40-70 years were analyzed. Given substantial heterogeneity in both etiology and outcomes in ASD, we utilized both group-level and subject-level analysis approaches to test for signs of atypical intracortical MC as estimated by T1w/T2w ratio.
RESULTS
Group-level analyses showed no significant differences in average T1w/T2w ratio or its associations with age between groups, but revealed significant positive main effects of age bilaterally, with T1w/T2w ratio increasing with age across much of the cortex. In subject-level analyses, participants were classified into subgroups based on presence or absence of clusters of aberrant T1w/T2w ratio, and lower neuropsychological function was observed in the ASD subgroup with atypically high T1w/T2w ratio in spatially heterogeneous cortical regions. These differences were observed across several neuropsychological domains, including overall intellectual functioning, processing speed, and aspects of executive function.
CONCLUSIONS
The group-level and subject-level approaches employed here demonstrate the value of examining inter-individual variability and provide important preliminary insights into relationships between brain structure and cognition in the second half of the lifespan in ASD, suggesting shared factors contributing to atypical intracortical myelin content and poorer cognitive outcomes for a subset of middle aged to older autistic adults. These atypicalities likely reflect diverse histories of neurodevelopmental deficits, and possible compensatory changes, compounded by processes of aging, and may serve as useful markers of vulnerability to further cognitive decline in older adults with ASD.
Topics: Humans; Male; Female; Magnetic Resonance Imaging; Aged; Middle Aged; Myelin Sheath; Autism Spectrum Disorder; Adult; Cerebral Cortex; Neuropsychological Tests; Aging
PubMed: 38849980
DOI: 10.1002/brb3.3594 -
Ear, Nose, & Throat Journal Jun 2024A variety of diseases can affect the nasal vestibule. It might be challenging to diagnose and treat a nasal vestibular tumor due to the anatomical characteristics of the...
A variety of diseases can affect the nasal vestibule. It might be challenging to diagnose and treat a nasal vestibular tumor due to the anatomical characteristics of the nasal vestibule. Neurilemmoma is a tumor derived from Schwann cells of the nerve sheath. Less than 4% of these tumors invade the nasal cavity and sinuses. Nasal vestibule neurilemmoma is rare, it is often overlooked when a mass discovered. The diagnosis of it is mainly based on clinical symptoms, nasal endoscopy, and imaging, The mainstay of treatment is complete resection surgery. Pathological examination provides the final diagnosis. We present a patient with nasal vestibule neurilemmoma who underwent a successful endoscopic surgery without cosmetic deformity, and discuss the clinical manifestations, histological features, imaging features, differential diagnosis, treatment options, then reviewed relevant literature of this rare benign lesion.
PubMed: 38847401
DOI: 10.1177/01455613241259284 -
Gut Microbes 2024Gut microbiota is responsible for essential functions in human health. Several communication axes between gut microbiota and other organs via neural, endocrine, and...
Gut microbiota is responsible for essential functions in human health. Several communication axes between gut microbiota and other organs via neural, endocrine, and immune pathways have been described, and perturbation of gut microbiota composition has been implicated in the onset and progression of an emerging number of diseases. Here, we analyzed peripheral nerves, dorsal root ganglia (DRG), and skeletal muscles of neonatal and young adult mice with the following gut microbiota status: a) germ-free (GF), b) gnotobiotic, selectively colonized with 12 specific gut bacterial strains (Oligo-Mouse-Microbiota, OMM12), or c) natural complex gut microbiota (CGM). Stereological and morphometric analyses revealed that the absence of gut microbiota impairs the development of somatic median nerves, resulting in smaller diameter and hypermyelinated axons, as well as in smaller unmyelinated fibers. Accordingly, DRG and sciatic nerve transcriptomic analyses highlighted a panel of differentially expressed developmental and myelination genes. Interestingly, the type III isoform of Neuregulin1 (NRG1), known to be a neuronal signal essential for Schwann cell myelination, was overexpressed in young adult GF mice, with consequent overexpression of the transcription factor Early Growth Response 2 (), a fundamental gene expressed by Schwann cells at the onset of myelination. Finally, GF status resulted in histologically atrophic skeletal muscles, impaired formation of neuromuscular junctions, and deregulated expression of related genes. In conclusion, we demonstrate for the first time a gut microbiota regulatory impact on proper development of the somatic peripheral nervous system and its functional connection to skeletal muscles, thus suggesting the existence of a novel 'Gut Microbiota-Peripheral Nervous System-axis.'
Topics: Animals; Gastrointestinal Microbiome; Neuromuscular Junction; Mice; Ganglia, Spinal; Germ-Free Life; Peripheral Nerves; Muscle, Skeletal; Mice, Inbred C57BL; Neuregulin-1; Male; Bacteria; Schwann Cells
PubMed: 38845453
DOI: 10.1080/19490976.2024.2363015 -
Frontiers in Neurology 2024To visualize and analyze the literature related to sciatic nerve injury treatment from January 2019 to December 2023, and summarize the current status, hotspots, and... (Review)
Review
OBJECTIVE
To visualize and analyze the literature related to sciatic nerve injury treatment from January 2019 to December 2023, and summarize the current status, hotspots, and development trends of research in this field.
METHODS
Using CiteSpace and VOSviewer software, we searched the Web of Science database for literature related to the treatment of sciatic nerve injury. Then we analyzed and plotted visualization maps to show the number of publications, countries, institutions, authors, keywords, references, and journals.
RESULTS
A total of 2,653 articles were included in the English database. The annual number of publications exceeded 230, and the citation frequency increased yearly. The United States and China were identified as high-influence nations in this field. Nantong University was the leading institution in terms of close cooperation among institutions. The authors Wang Yu had the highest number of publications and were highly influential in this field. Keyword analysis and reference Burst revealed a research focus on nerve regeneration and neuropathic pain, which involve regenerative medicine and neural tissue engineering. Chronic pain resulting from sciatic nerve injury often manifests alongside anxiety, depression, cognitive-behavioral disorders, and other issues. Interventions such as stem cells, electrical stimulation, electroacupuncture, total joint replacement, pharmacological interventions, gene therapy, nerve conduits, chitosan scaffolds, and exercise promote nerve repair and alleviate pain. Schwann cells have been the focus of much attention in nerve repair and regeneration. Improving the outcome of sciatic nerve injury is a current research challenge and focus in this field. Based on keyword Burst, nerve conduits and grafts may become a potential research hotspot in the treatment of sciatic nerve injury.
CONCLUSION
This visual analysis summarizes research trends and developments of sciatic nerve injury treatment and predicts potential research frontiers and hot directions.
PubMed: 38841698
DOI: 10.3389/fneur.2024.1378689 -
ENeuro Jun 2024Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use respiratory epithelial cells as an entry point for infection. Within the nasal cavity,...
Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use respiratory epithelial cells as an entry point for infection. Within the nasal cavity, the olfactory epithelium (OE) is particularly sensitive to infections which may lead to olfactory dysfunction. In patients suffering from coronavirus disease 2019, deficits in olfaction have been characterized as a distinctive symptom. Here, we used the K18hACE2 mice to study the spread of SARS-CoV-2 infection and inflammation in the olfactory system (OS) after 7 d of infection. In the OE, we found that SARS-CoV-2 selectively targeted the supporting/sustentacular cells (SCs) and macrophages from the lamina propria. In the brain, SARS-CoV-2 infected some microglial cells in the olfactory bulb (OB), and there was a widespread infection of projection neurons in the OB, piriform cortex (PC), and tubular striatum (TuS). Inflammation, indicated by both elevated numbers and morphologically activated IBA1 cells (monocyte/macrophage lineages), was preferentially increased in the OE septum, while it was homogeneously distributed throughout the layers of the OB, PC, and TuS. Myelinated OS axonal tracts, the lateral olfactory tract, and the anterior commissure, exhibited decreased levels of 2',3'-cyclic-nucleotide 3'-phosphodiesterase, indicative of myelin defects. Collectively, our work supports the hypothesis that SARS-CoV-2 infected SC and macrophages in the OE and, centrally, microglia and subpopulations of OS neurons. The observed inflammation throughout the OS areas and central myelin defects may account for the long-lasting olfactory deficit.
Topics: Animals; COVID-19; Mice; Olfactory Mucosa; Olfactory Bulb; SARS-CoV-2; Myelin Sheath; Microglia; Mice, Transgenic; Angiotensin-Converting Enzyme 2; Olfaction Disorders; Disease Models, Animal; Male; Inflammation; Macrophages; Female
PubMed: 38834299
DOI: 10.1523/ENEURO.0106-24.2024 -
Journal of Surgical Case Reports Jun 2024Granular cell tumors are rare soft tissue neoplasms derived from Schwann cells and are characterized by their infiltrative, non-encapsulated nests and sheets of...
Granular cell tumors are rare soft tissue neoplasms derived from Schwann cells and are characterized by their infiltrative, non-encapsulated nests and sheets of polygonal cells with fine eosinophilic cytoplasmic granules on histology. Herin, we report a case of a 10-year-old Saudi female who presented to the hospital with multiple asymptomatic skin lesions, the largest located on the right shoulder and left foot. Preoperative workup revealed the absence of liver metastasis, and the patient underwent complete surgical excision successfully. Histopathology revealed ill-defined proliferation of large bland cells with prominent eosinophilic granular cytoplasm and mild epithelial hyperplasia consistent with granular cell tumors. Granular cell tumors are a rare entity that represent only 0.5% of all soft tissue tumors. They have characteristic histological features and can present with both malignant and being features. Due to the rarity of this disease, further research is needed to enhance our understanding and improve recognition in future practice.
PubMed: 38832053
DOI: 10.1093/jscr/rjae384