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Journal of Neurochemistry Jul 2023Schwann cells (SCs) support peripheral nerves under homeostatic conditions, independent of myelination, and contribute to damage in prediabetic peripheral neuropathy...
Schwann cells (SCs) support peripheral nerves under homeostatic conditions, independent of myelination, and contribute to damage in prediabetic peripheral neuropathy (PN). Here, we used single-cell RNA sequencing to characterize the transcriptional profiles and intercellular communication of SCs in the nerve microenvironment using the high-fat diet-fed mouse, which mimics human prediabetes and neuropathy. We identified four major SC clusters, myelinating, nonmyelinating, immature, and repair in healthy and neuropathic nerves, in addition to a distinct cluster of nerve macrophages. Myelinating SCs acquired a unique transcriptional profile, beyond myelination, in response to metabolic stress. Mapping SC intercellular communication identified a shift in communication, centered on immune response and trophic support pathways, which primarily impacted nonmyelinating SCs. Validation analyses revealed that neuropathic SCs become pro-inflammatory and insulin resistant under prediabetic conditions. Overall, our study offers a unique resource for interrogating SC function, communication, and signaling in nerve pathophysiology to help inform SC-specific therapies.
Topics: Mice; Humans; Animals; Myelin Sheath; Prediabetic State; Single-Cell Gene Expression Analysis; Schwann Cells; Peripheral Nerves; Peripheral Nervous System Diseases
PubMed: 37328915
DOI: 10.1111/jnc.15877 -
Journal of the Peripheral Nervous... Sep 2023Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be... (Review)
Review
BACKGROUND AND AIMS
Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be neurotoxic. There are concerns about the use of these drugs in patients with Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy. This review provides evidence-based updated recommendations on this clinically relevant topic.
METHODS
A systematic review of the available studies/reports written in English was performed from July to September 2022 including in the search string all reported putative neurotoxic drugs.
RESULTS
The results of our systematic review provide evidence-based support for the statement that use of vincristine, and possibly paclitaxel, can occasionally induce an atypical, and more severe, course of drug-related peripheral neurotoxicity in CMT patients. It is therefore reasonable to recommend caution in the use of these compounds in CMT patients. However, no convincing evidence for a similar recommendation could be found for all other drugs.
INTERPRETATION
It is important that patients with CMT are not denied effective treatments that may prolong life expectancy for cancer or improve their health status if affected by non-oncological diseases. Accurate monitoring of peripheral nerve function in CMT patients treated with any neurotoxic agent remains mandatory to detect the earliest signs of neuropathy worsening and atypical clinical courses. Neurologists monitoring CMT patients as part of their normal care package or for natural history studies should keep detailed records of exposures to neurotoxic medications and support reporting of accelerated neuropathy progression if observed.
Topics: Humans; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Neoplasms; Neurotoxicity Syndromes
PubMed: 37249082
DOI: 10.1111/jns.12566 -
Phytotherapy Research : PTR Dec 2023Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose...
Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.
Topics: Rats; Animals; AMP-Activated Protein Kinases; Diabetes Mellitus, Experimental; Sirtuin 1; Ferroptosis; Peripheral Nervous System Diseases; Schwann Cells; Glucose
PubMed: 37580045
DOI: 10.1002/ptr.7984 -
Journal of the Peripheral Nervous... Jul 2023The nodes of Ranvier (NoR) are essential domains for nerve conduction and their disruption plays a key role in the pathophysiology of immune-mediated neuropathies. Our... (Review)
Review
The nodes of Ranvier (NoR) are essential domains for nerve conduction and their disruption plays a key role in the pathophysiology of immune-mediated neuropathies. Our understanding of the specialized nodal regions and the immune mechanisms that affect them is growing and has led to the update of peripheral neuropathy classification to include the autoimmune nodopathies, defined by the site of the autoimmune attack. Autoantibodies directed against molecules of the nodal region (as neurofascin-140/186, neurofascin-155, contactin-1, contactin-associated protein 1, contactin-associated protein 2, gangliosides, LGI4, or myelin-associated glycoprotein), macrophage-induced paranodal demyelination, and phenotypic changes of the nodal domains of Schwann cells have been identified as key mechanisms in the pathogenesis of the autoimmune neuropathies. This review explores the current knowledge of the autoimmune vulnerability of the NoR, including the underlying mechanisms leading to dysfunction in the diverse autoimmune disorders.
Topics: Humans; Ranvier's Nodes; Schwann Cells; Peripheral Nervous System Diseases; Autoantibodies; Contactins
PubMed: 37272737
DOI: 10.1111/jns.12570 -
Handbook of Clinical Neurology 2024Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality... (Review)
Review
Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality subgroup. Symptoms include weakness, sensory loss, sweating irregularity, blood pressure instability, severe constipation, and neuropathic pain. Neuropathy is the first presenting symptom of malignancy among many patients. The molecular and cellular oncogenic immune targets reside within cell bodies, axons, cytoplasms, or surface membranes of neural tissues. A more favorable immune treatment outcome occurs in those where the targets reside on the cell surface. Patients with antibodies binding cell surface antigens commonly have neural hyperexcitability with pain, cramps, fasciculations, and hyperhidrotic attacks (CASPR2, LGI1, and others). The antigenic targets are also commonly expressed in the central nervous system, with presenting symptoms being myelopathy, encephalopathy, and seizures with neuropathy, often masked. Pain and autonomic components typically relate to small nerve fiber involvement (nociceptive, adrenergic, enteric, and sudomotor), sometimes without nerve fiber loss but rather hyperexcitability. The specific antibodies discovered help direct cancer investigations. Among the primary axonal paraneoplastic neuropathies, pathognomonic clinical features do not exist, and testing for multiple antibodies simultaneously provides the best sensitivity in testing (AGNA1-SOX1; amphiphysin; ANNA-1-HU; ANNA-3-DACH1; CASPR2; CRMP5; LGI1; PCA2-MAP1B, and others). Performing confirmatory antibody testing using adjunct methods improves specificity. Antibody-mediated demyelinating paraneoplastic neuropathies are limited to MAG-IgM (IgM-MGUS, Waldenström's, and myeloma), with the others associated with cytokine elevations (VEGF, IL6) caused by osteosclerotic myeloma, plasmacytoma (POEMS), and rarely angiofollicular lymphoma (Castleman's). Paraneoplastic disorders have clinical overlap with other idiopathic antibody disorders, including IgG4 demyelinating nodopathies (NF155 and Contactin-1). This review summarizes the paraneoplastic neuropathies, including those with peripheral nerve hyperexcitability.
Topics: Humans; Paraneoplastic Polyneuropathy; Multiple Myeloma; Peripheral Nervous System Diseases; Isaacs Syndrome; Autoantibodies; Peripheral Nerves; Immunoglobulin M; Pain
PubMed: 38494281
DOI: 10.1016/B978-0-12-823912-4.00020-7 -
The Journal of Hand Surgery Mar 2024Amyloidosis can lead to cardiac, renal, and other multiorgan failure. New treatments have become available that can prolong survival but rely on early diagnosis.... (Review)
Review
Amyloidosis can lead to cardiac, renal, and other multiorgan failure. New treatments have become available that can prolong survival but rely on early diagnosis. Manifestations of amyloidosis in hand surgery include carpal tunnel syndrome, trigger finger, peripheral neuropathy, and spontaneous distal biceps rupture. Often, these can predate systemic amyloidosis, offering hand surgeons an opportunity to diagnose patients with amyloidosis before systemic disease, refer them for treatment, and potentially alter disease course and prolong survival. In this review, we describe the pathophysiology and two most common subtypes of amyloidosis seen by hand surgeons. We provide guidance on biopsy practices and referral for patients with amyloidosis. Lastly, we provide a brief overview of the treatments for amyloidosis and their effect on disease course.
Topics: Humans; Amyloidosis; Carpal Tunnel Syndrome; Peripheral Nervous System Diseases; Trigger Finger Disorder; Surgeons
PubMed: 38043036
DOI: 10.1016/j.jhsa.2023.10.013 -
Expert Review of Neurotherapeutics 2023Guillain-Barré syndrome (GBS) is an immune-mediated poly(radiculo)neuropathy with a variable clinical outcome. Identifying patients who are at risk of suffering from... (Review)
Review
INTRODUCTION
Guillain-Barré syndrome (GBS) is an immune-mediated poly(radiculo)neuropathy with a variable clinical outcome. Identifying patients who are at risk of suffering from long-term disabilities is a great challenge. Biomarkers are useful to confirm diagnosis, monitor disease progression, and predict outcome.
AREAS COVERED
The authors provide an overview of the diagnostic and prognostic biomarkers for GBS, which are useful for establishing early treatment strategies and follow-up care plans.
EXPERT OPINION
Detecting patients at risk of developing a severe outcome may improve management of disease progression and limit potential complications. Several clinical factors are associated with poor prognosis: higher age, presence of diarrhea within 4 weeks of symptom onset, rapid and severe weakness progression, dysautonomia, decreased vital capacity and facial, bulbar, and neck weakness. Biological, neurophysiological and imaging measures of unfavorable outcome include multiple anti-ganglioside antibodies elevation, increased serum and CSF neurofilaments light (NfL) and heavy chain, decreased NfL CSF/serum ratio, hypoalbuminemia, nerve conduction study with early signs of demyelination or axonal loss and enlargement of nerve cross-sectional area on ultrasound. Depicting prognostic biomarkers aims at predicting short-term mortality and need for cardio-pulmonary support, long-term patient functional outcome, guiding treatment decisions and monitoring therapeutic responses in future clinical trials.
Topics: Humans; Infant, Newborn; Guillain-Barre Syndrome; Biomarkers; Autonomic Nervous System Diseases; Disease Progression
PubMed: 37902064
DOI: 10.1080/14737175.2023.2273386 -
Revue Neurologique Oct 2023Autoimmune neuropathies are a heterogeneous group of rare and disabling diseases in which the immune system targets peripheral nervous system antigens and that respond... (Review)
Review
Autoimmune neuropathies are a heterogeneous group of rare and disabling diseases in which the immune system targets peripheral nervous system antigens and that respond to immune therapies. This review focuses on Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, polyneuropathy associated with IgM monoclonal gammopathy, and autoimmune nodopathies. Autoantibodies targeting gangliosides, proteins in the node of Ranvier, and myelin-associated glycoprotein have been described in these disorders, defining subgroups of patients with similar clinical features and response to therapy. This topical review describes the role of these autoantibodies in the pathogenesis of autoimmune neuropathies and their clinical and therapeutic importance.
Topics: Humans; Autoantibodies; Guillain-Barre Syndrome; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Polyneuropathies
PubMed: 36907709
DOI: 10.1016/j.neurol.2023.02.064 -
Molecular Medicine (Cambridge, Mass.) Jul 2023Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound...
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN.
METHODS
Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected.
RESULTS
CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs.
CONCLUSIONS
CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.
Topics: Rats; Animals; Diabetic Neuropathies; Rats, Sprague-Dawley; Endoplasmic Reticulum Stress; Myelin Sheath; Signal Transduction; Sciatic Nerve; Diabetes Mellitus
PubMed: 37464341
DOI: 10.1186/s10020-023-00698-3 -
Handbook of Clinical Neurology 2024Electrodiagnostic testing (EDX) has been the diagnostic tool of choice in peripheral nerve disease for many years, but in recent years, peripheral nerve imaging has been... (Review)
Review
Electrodiagnostic testing (EDX) has been the diagnostic tool of choice in peripheral nerve disease for many years, but in recent years, peripheral nerve imaging has been used ever more frequently in daily clinical practice. Nerve ultrasound and magnetic resonance (MR) neurography are able to visualize nerve structures reliably. These techniques can aid in localizing nerve pathology and can reveal significant anatomical abnormalities underlying nerve pathology that may have been otherwise undetected by EDX. As such, nerve ultrasound and MR neurography can significantly improve diagnostic accuracy and can have a significant effect on treatment strategy. In this chapter, the basic principles and recent developments of these techniques will be discussed, as well as their potential application in several types of peripheral nerve disease, such as carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow (UNE), radial neuropathy, brachial and lumbosacral plexopathy, neuralgic amyotrophy (NA), fibular, tibial, sciatic, femoral neuropathy, meralgia paresthetica, peripheral nerve trauma, tumors, and inflammatory neuropathies.
Topics: Humans; Peripheral Nervous System Diseases; Ultrasonography; Magnetic Resonance Imaging; Electrodiagnosis
PubMed: 38697740
DOI: 10.1016/B978-0-323-90108-6.00001-6