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37/67 kDa laminin receptor (LamR)/ribosomal protein SA exhibits dual function as both a ribosomal protein and cell surface receptor for laminin. LamR influences critical cellular processes such as invasion, adhesion, and migration when acting as a receptor. Despite the acknowledged importance of LamR/67LR in various cellular processes, its contribution to the peripheral nervous system development is obscure. Thus, this study investigated the biological activity of LamR in peripheral axonal outgrowth in the presence of laminin-1 or Ile-Lys-Val-Ala- Val (IKVAV) peptide, whose important role in dorsal root ganglia (DRG) axonal outgrowth we recently showed. Unexpectedly, we did not observe LamR on the surface of DRG cells or in a conditioned medium, suggesting its intracellular action in the negative regulation of DRG axonal outgrowth. Using C-terminus LamR-targeting IgG, we demonstrated the role of LamR in that process, which is independent of the presence of Schwann cell precursors (SCPs) and is mediated by extracellular signal-regulated kinase (Erk) and Protein kinase B (Akt1/2/3) signaling pathways. Additionally, we show that the action of LamR towards laminin-1-dependent axonal outgrowth is unmasked only when the activity of integrin β1 is perturbed. We believe that modulation of LamR activity provides the basis for its use for inhibiting axon growth as a potential therapeutic agent for regulating abnormal or excessive neurite growth during neurodevelopmental diseases or pathological nerve regeneration. [ABSTRACT FROM AUTHOR]

Gene delivery or manipulation with viral vectors is a frequently used tool in basic neuroscience studies. Adeno-associated viruses (AAV) are the most widely used vectors due to their relative safety and long-term efficacy without causing overt immunological complications. Many AAV serotypes have been discovered and engineered that preferentially transduce different populations of neurons. However, efficient targeting of peripheral neurons remains challenging for many researchers, and evaluation of peripheral neuron transduction with AAVs in rats is limited. Here, we aimed to test the efficiency of systemic AAVs to transduce peripheral neurons in rats. We administered AAV9-tdTomato, AAV-PHP.S-tdTomato, or AAV-retro-GFP systemically to neonatal rats via intraperitoneal injection. After 5 weeks, we evaluated expression patterns in peripheral sensory, motor, and autonomic neurons. No significant difference between the serotypes in the transduction of sensory neurons was noted, and all serotypes were more efficient in transducing NF200 + neurons compared to smaller CGRP + neurons. AAV-retro was more efficient at transducing motor neurons compared to other serotypes. Moreover, PHP.S was more efficient at transducing sympathetic neurons, and AAV-retro was more efficient at transducing parasympathetic neurons. These results indicate that specific AAV serotypes target peripheral neuron populations more efficiently than others in the neonatal rat.

37/67 kDa laminin receptor (LamR)/ribosomal protein SA exhibits dual function as both a ribosomal protein and cell surface receptor for laminin. LamR influences critical cellular processes such as invasion, adhesion, and migration when acting as a receptor. Despite the acknowledged importance of LamR/67LR in various cellular processes, its contribution to the peripheral nervous system development is obscure. Thus, this study investigated the biological activity of LamR in peripheral axonal outgrowth in the presence of laminin-1 or Ile-Lys-Val-Ala-Val (IKVAV) peptide, whose important role in dorsal root ganglia (DRG) axonal outgrowth we recently showed. Unexpectedly, we did not observe LamR on the surface of DRG cells or in a conditioned medium, suggesting its intracellular action in the negative regulation of DRG axonal outgrowth. Using C-terminus LamR-targeting IgG, we demonstrated the role of LamR in that process, which is independent of the presence of Schwann cell precursors (SCPs) and is mediated by extracellular signal-regulated kinase (Erk) and Protein kinase B (Akt1/2/3) signaling pathways. Additionally, we show that the action of LamR towards laminin-1-dependent axonal outgrowth is unmasked only when the activity of integrin β1 is perturbed. We believe that modulation of LamR activity provides the basis for its use for inhibiting axon growth as a potential therapeutic agent for regulating abnormal or excessive neurite growth during neurodevelopmental diseases or pathological nerve regeneration.

The interaction between the central nervous system (CNS) and peripheral nervous system (PNS) governs various physiological functions, influences cognitive processes and emotional states. It is necessary to unravel the mechanisms governing the interaction between the brain and the body, enhancing our understanding of physical and mental well-being. Neuro-ergonomics-based human-computer interaction can be improved by comprehending the intricate interrelation between the CNS and PNS. Various studies have been explored using diverse methodologies to study CNS-PNS interaction in specific psychophysiological states, such as emotion, stress, or cognitive tasks. However, there is a need for a thorough, extensive, and systematic review covering diverse interaction forms, applications, and assessments. In this work, an attempt has been made to perform a systematic review that examines the interaction between the CNS and PNS across diverse psychophysiological states, focusing on varied physiological signals. For this, scientific repositories, namely Scopus, PubMed, Association for Computing Machinery, and Web of Science, are accessed. In total, 61 articles have been identified within the period of January 2008 to April 2023 for systematic review. The selected research articles are analyzed based on factors, namely subject information, stimulation modality, types of interactions between the brain and other organs, feature extraction techniques, classification methods, and statistical approaches. The evaluation of the existing literature indicates a scarcity of publicly available databases for CNS-PNS interaction and limited application of machine learning and deep learning-based advanced tools. Furthermore, this review underscores the urgent need for enhancements in several key areas including the development of a more refined psycho-physiological model, improved analysis techniques, and better electrode-surface interface technology. Additionally, there is a need for more research involving daily life activities, female-oriented studies, and privacy considerations. This review contributes to standardizing protocols, improves the diagnostic relevance of various instruments, and extracts more reliable biomarkers. The novelty of this study lies in guiding researchers to point out various issues and potential solutions for future research in the field of bio-signal-based CNS-PNS interaction.

Sensory neurons (SNs) detect a wide range of information from the body and the environment that is critical for homeostasis. There are three main subtypes of SNs: nociceptors, mechanoreceptors, and proprioceptors, which express different membrane proteins, such as TRKA, TRKB, or TRKC, respectively. Human pluripotent stem cell technology provides an ideal platform to study development and diseases of SNs, however there is not a viable method to isolate individual SN subtype for downstream analysis available. Here, we employ the method immunopanning to isolate each SN subtype. This method is very gentle and allows proper survival after the isolation. We use antibodies against TRKA, TRKB, and TRKC to isolate nociceptors, mechanoreceptors, and proprioceptors, respectively. We show that our cultures are enriched for each subtype and express their respective subtype markers. Furthermore, we show that the immunopanned SNs are electrically active and respond to specific stimuli. Thus, our method can be used to purify viable neuronal subtypes using respective membrane proteins for downstream studies.

Gene delivery or manipulation with viral vectors is a frequently used tool in basic neuroscience studies. Adeno-associated viruses (AAV) are the most widely used vectors due to their relative safety and long-term efficacy without causing overt immunological complications. Many AAV serotypes have been discovered and engineered that preferentially transduce different populations of neurons. However, efficient targeting of peripheral neurons remains challenging for many researchers, and evaluation of peripheral neuron transduction with AAVs in rats is limited. Here, we aimed to test the efficiency of systemic AAVs to transduce peripheral neurons in rats. We administered AAV9-tdTomato, AAV-PHP.S-tdTomato, or AAV-retro-GFP systemically to neonatal rats via intraperitoneal injection. After 5 weeks, we evaluated expression patterns in peripheral sensory, motor, and autonomic neurons. No significant difference between the serotypes in the transduction of sensory neurons was noted, and all serotypes were more efficient in transducing NF200 + neurons compared to smaller CGRP + neurons. AAV-retro was more efficient at transducing motor neurons compared to other serotypes. Moreover, PHP.S was more efficient at transducing sympathetic neurons, and AAV-retro was more efficient at transducing parasympathetic neurons. These results indicate that specific AAV serotypes target peripheral neuron populations more efficiently than others in the neonatal rat. [ABSTRACT FROM AUTHOR]

Gene delivery or manipulation with viral vectors is a frequently used tool in basic neuroscience studies. Adeno-associated viruses (AAV) are the most widely used vectors due to their relative safety and long-term efficacy without causing overt immunological complications. Many AAV serotypes have been discovered and engineered that preferentially transduce different populations of neurons. However, efficient targeting of peripheral neurons remains challenging for many researchers, and evaluation of peripheral neuron transduction with AAVs in rats is limited. Here, we aimed to test the efficiency of systemic AAVs to transduce peripheral neurons in rats. We administered AAV9-tdTomato, AAV-PHP.S-tdTomato, or AAV-retro-GFP systemically to neonatal rats via intraperitoneal injection. After 5 weeks, we evaluated expression patterns in peripheral sensory, motor, and autonomic neurons. No significant difference between the serotypes in the transduction of sensory neurons was noted, and all serotypes were more efficient in transducing NF200 + neurons compared to smaller CGRP + neurons. AAV-retro was more efficient at transducing motor neurons compared to other serotypes. Moreover, PHP.S was more efficient at transducing sympathetic neurons, and AAV-retro was more efficient at transducing parasympathetic neurons. These results indicate that specific AAV serotypes target peripheral neuron populations more efficiently than others in the neonatal rat.

Parsonage-Turner Syndrome (PTS), also known as brachial neuritis or neuralgic amyotrophy, is a rare disorder affecting 2 to 3 individuals per 100,000 each year. Abrupt onset shoulder pain, followed by motor weakness, paresthesia and hypoesthesia, is usually reported, lasting several months with variable recovery. The etiology of the disease may be idiopathic or triggered by an underlying autoimmune disease in genetically susceptible individuals. Our report addresses a unique case of Parsonage-Turner Syndrome in a patient suffering from concurrent Hashimoto Thyroiditis. A previously healthy A 22 year-old female was referred to the Department of Neurology after complaints of sudden-onset motor weakness in her left upper limb. On physical examination, the patient could not make an “Ok sign” with her thumb and distal phalanx or form a complete fist, revealing weakness within the anterior interosseous branch of the median nerve. Further testing with electromyography demonstrated muscular atrophy within the arm's anterior compartment, forearm, and triceps brachii of the posterior compartment. Additional imaging and physical examination were unremarkable, confirming our diagnosis of PTS. Furthermore, lab reports revealed elevated levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies and our patient was concurrently diagnosed with Hashimoto's thyroiditis.This case aims to highlight the rare co-occurrence of Hashimoto's thyroiditis with Parsonage-Turner Syndrome in an otherwise healthy patient. A 2014 study published by Nugent et al. had also shed light on brachial neuritis in a patient suffering from autoimmune connective tissue disease, and through this case study, we hope to add to the growing literature regarding the correlation between PTS and autoimmune diseases. Symptoms of PTS can easily be misdiagnosed given its similarity to other peripheral neuropathies, and careful assessment and thorough understanding of the disease is required to successfully distinguish it from other neurological pathologies.

Significance: Reactive oxygen species (ROS) contribute to multiple aspects of peripheral nervous system (PNS) biology ranging from physiological processes (e.g., axonal outgrowth and regeneration) to pathophysiology (e.g., nerve degeneration). Although ROS are derived from multiple sources, NADPH oxidase (Nox) family members are dedicated to ROS generation. Noxs are expressed in the PNS, and their overexpression is associated with detrimental effects on nerve function and contributes, at least in part, to peripheral neuropathies. Recent Advances: Of the seven members, studies mostly focused on Nox1, Nox2, and Nox4, which are expressed in the PNS in a cell-specific manner. We have also recently identified human Nox5 in sural nerve biopsies. When maintained at homeostatic levels, Noxs regulate several aspects of peripheral nerve health, most notably neurite outgrowth and axonal regeneration following nerve lesion. While Nox2 and Nox4 dysregulation is a major source of oxidative stress in PNS disorders, including neuropathic pain and diabetic peripheral neuropathy, recent evidence also implicates Nox1 and Nox5. Critical Issues: Although there is compelling evidence for a direct role of Noxs on nerve function, little is known about their subcellular localization, intercellular regulation, and interaction. These, together with redox signaling, are considered crucial components of nerve redox status. In addition, the lack of isoform-specific inhibitors limits conclusions about the physiological role of Noxs in the PNS and their therapeutic potential in peripheral neuropathies. Future Directions: Future research using isoform-specific genetic and pharmacological approaches are therefore needed to better understand the significance of Nox enzymes in PNS (patho) physiology. Antioxid. Redox Signal. 37, 613–630. [ABSTRACT FROM AUTHOR]

The stimulating peripheral activity to relieve conditions (SPARC) program is a US National Institutes of Health-funded effort to improve our understanding of the neural circuitry of the autonomic nervous system (ANS) in support of bioelectronic medicine. As part of this effort, the SPARC project is generating multi-species, multimodal data, models, simulations, and anatomical maps supported by a comprehensive knowledge base of autonomic circuitry. To facilitate the organization of and integration across multi-faceted SPARC data and models, SPARC is implementing the findable, accessible, interoperable, and reusable (FAIR) data principles to ensure that all SPARC products are findable, accessible, interoperable, and reusable. We are therefore annotating and describing all products with a common FAIR vocabulary. The SPARC Vocabulary is built from a set of community ontologies covering major domains relevant to SPARC, including anatomy, physiology, experimental techniques, and molecules. The SPARC Vocabulary is incorporated into tools researchers use to segment and annotate their data, facilitating the application of these ontologies for annotation of research data. However, since investigators perform deep annotations on experimental data, not all terms and relationships are available in community ontologies. We therefore implemented a term management and vocabulary extension pipeline where SPARC researchers may extend the SPARC Vocabulary using InterLex, an online vocabulary management system. To ensure the quality of contributed terms, we have set up a curated term request and review pipeline specifically for anatomical terms involving expert review. Accepted terms are added to the SPARC Vocabulary and, when appropriate, contributed back to community ontologies to enhance ANS coverage. Here, we provide an overview of the SPARC Vocabulary, the infrastructure and process for implementing the term management and review pipeline. In an analysis of >300 anatomical contributed terms, the majority represented composite terms that necessitated combining terms within and across existing ontologies. Although these terms are not good candidates for community ontologies, they can be linked to structures contained within these ontologies. We conclude that the term request pipeline serves as a useful adjunct to community ontologies for annotating experimental data and increases the FAIRness of SPARC data. [ABSTRACT FROM AUTHOR]

The stimulating peripheral activity to relieve conditions (SPARC) program is a US National Institutes of Health-funded effort to improve our understanding of the neural circuitry of the autonomic nervous system (ANS) in support of bioelectronic medicine. As part of this effort, the SPARC project is generating multi-species, multimodal data, models, simulations, and anatomical maps supported by a comprehensive knowledge base of autonomic circuitry. To facilitate the organization of and integration across multi-faceted SPARC data and models, SPARC is implementing the findable, accessible, interoperable, and reusable (FAIR) data principles to ensure that all SPARC products are findable, accessible, interoperable, and reusable. We are therefore annotating and describing all products with a common FAIR vocabulary. The SPARC Vocabulary is built from a set of community ontologies covering major domains relevant to SPARC, including anatomy, physiology, experimental techniques, and molecules. The SPARC Vocabulary is incorporated into tools researchers use to segment and annotate their data, facilitating the application of these ontologies for annotation of research data. However, since investigators perform deep annotations on experimental data, not all terms and relationships are available in community ontologies. We therefore implemented a term management and vocabulary extension pipeline where SPARC researchers may extend the SPARC Vocabulary using InterLex, an online vocabulary management system. To ensure the quality of contributed terms, we have set up a curated term request and review pipeline specifically for anatomical terms involving expert review. Accepted terms are added to the SPARC Vocabulary and, when appropriate, contributed back to community ontologies to enhance ANS coverage. Here, we provide an overview of the SPARC Vocabulary, the infrastructure and process for implementing the term management and review pipeline. In an analysis of >300 anatomical contributed terms, the majority represented composite terms that necessitated combining terms within and across existing ontologies. Although these terms are not good candidates for community ontologies, they can be linked to structures contained within these ontologies. We conclude that the term request pipeline serves as a useful adjunct to community ontologies for annotating experimental data and increases the FAIRness of SPARC data.

Although the pathogenic operations of cancer–nerve crosstalk (e.g., neuritogenesis, neoneurogensis, and perineural invasion—PNI) in the peripheral nervous system (PNS) during tumorigenesis, as well as the progression of all cancer types is continuing to emerge as an area of unique scientific interest and study, extensive, wide-ranging, and multidisciplinary investigations still remain fragmented and unsystematic. This is especially so in regard to the roles played by extracellular vesicles (EVs), which are lipid bilayer-enclosed nano- to microsized particles that carry multiple-function molecular cargos, facilitate intercellular communication in diverse processes. Accordingly, the biological significance of EVs has been greatly elevated in recent years, as there is strong evidence that they could contribute to important and possibly groundbreaking diagnostic and therapeutic innovations. This can be achieved and the pace of discoveries accelerated through cross-pollination from existing knowledge and studies regarding nervous system physiology and pathology, as well as thoroughgoing collaborations between oncologists, neurobiologists, pathologists, clinicians, and researchers. This article offers an overview of current and recent past investigations on the roles of EVs in cancer–nerve crosstalk, as well as in neural development, physiology, inflammation, injury, and regeneration in the PNS. By highlighting the mechanisms involved in physiological and noncancerous pathological cellular crosstalk, we provide hints that may inspire additional translational studies on cancer–nerve interplay. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms. Aim: The purpose of this study was to assess PNS damage at the lumbar plexus and sciatic nerve anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS. Method: Eleven HCs (7 female, mean age 33.6 years, range 24-50) and 15 people with RRMS (12 female, mean age 38.5 years, range 30-56) were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS. Results: MTR values in the sciatic nerve of people with RRMS were found to be significantly lower compared to HCs, but no significant MTR changes were identified in the lumbar plexus of people with RRMS. The median EDSS in people with RRMS was 2.0 (range, 0-3). No relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS. Conclusion: The results from this study demonstrate the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS. Further investigations to confirm these findings and to clarify the pathophysiological basis of these alterations are warranted. [ABSTRACT FROM AUTHOR]

An active probe and microstimulator SoC for interfacing with peripheral nerves is presented. It performs 64-channel artifact-tolerant neural recording, cuff imbalance compensation by impedance sensing, and neurostimulation for the closed-loop operation. Each recording channel is a second-order opamp-less $\Delta \Sigma $ ADC that consumes 140 nW and occupies 0.01 mm2 area in 130 nm CMOS. The single-loop $\Delta \Sigma $ architecture achieves second-order noise shaping with two passive integrators. To the best of our knowledge, this yields the lowest power and area of any second-order $\Delta \Sigma $ ADC and the lowest FOM (fJ/conv. step) of any passive second-order $\Delta \Sigma $ ADC (27 fJ/conv. step). The SoC uniquely performs multi-modal input signal recording: voltage (for neural recording) and current (for impedance sensing) are measured concurrently using frequency multiplexing. The SoC also features a 60 MHz energy-efficient inductive powering link and a 600 MHz RF data communication link. The prototype is validated in vivo in the rat sciatic nerve for electroneurogram (ENG) sensing and the correction of impedance-imbalance in cuff electrodes. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms.Aim: The purpose of this study was to assess PNS damage at the lumbar plexus and sciatic nerve anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS.Method: Eleven HCs (7 female, mean age 33.6 years, range 24-50) and 15 people with RRMS (12 female, mean age 38.5 years, range 30-56) were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS.Results: MTR values in the sciatic nerve of people with RRMS were found to be significantly lower compared to HCs, but no significant MTR changes were identified in the lumbar plexus of people with RRMS. The median EDSS in people with RRMS was 2.0 (range, 0-3). No relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS.Conclusion: The results from this study demonstrate the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS. Further investigations to confirm these findings and to clarify the pathophysiological basis of these alterations are warranted.

Cellular metabolism is critical not only for cell survival, but also for cell fate, function, and intercellular communication. There are several different metabolic transporters expressed in the peripheral nervous system, and they each play important roles in maintaining cellular energy. The major source of energy in the peripheral nervous system is glucose, and glucose transporters 1 and 3 are expressed and allow blood glucose to be imported and utilized by peripheral nerves. There is also increasing evidence that other sources of energy, particularly monocarboxylates such as lactate that are transported primarily by monocarboxylate transporters 1 and 2 in peripheral nerves, can be efficiently utilized by peripheral nerves. Finally, emerging evidence supports an important role for connexins and possibly pannexins in the supply and regulation of metabolic energy. In this review, we will first define these critical metabolic transporter subtypes and then examine their localization in the peripheral nervous system. We will subsequently discuss the evidence, which comes both from experiments in animal models and observations from human diseases, supporting critical roles played by these metabolic transporters in the peripheral nervous system. Despite progress made in understanding the function of these transporters, many questions and some discrepancies remain, and these will also be addressed throughout this review. Peripheral nerve metabolism is fundamentally important and renewed interest in these pathways should help to answer many of these questions and potentially provide new treatments for neurologic diseases that are partly, or completely, caused by disruption of metabolism. [ABSTRACT FROM AUTHOR]

The bHLH transcription factor Olig2 is required for sequential cell fate determination of both motor neurons and oligodendrocytes and for progenitor proliferation in the central nervous system. However, the role of Olig2 in peripheral sensory neurogenesis remains unknown. We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice, associated with significantly diminished expression of multiple OSN maturation and odorant signaling genes, including Omp, Gnal, Adcy3, and Olfr15. We further demonstrate that Olig2 binds to the E-box in the Omp promoter region to regulate its expression. Taken together, our results reveal a distinctly novel function of Olig2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons. [ABSTRACT FROM AUTHOR]

Integrin-linked kinase (ILK) is mainly localized in focal adhesions where it interacts and modulates the downstream signaling of integrins affecting cell migration, adhesion, and survival. The interaction of dorsal root ganglia (DRG) cells, being part of the peripheral nervous system (PNS), with the extracellular matrix (ECM) via integrins is crucial for proper PNS development. A few studies have focused on ILK’s role in PNS development, but none of these have focused on chicken. Therefore, we decided to investigate ILK’s role in the development of Gallus gallus domesticus’s DRG. First, using RT-PCR, Western blotting, and in situ hybridization, we show that ILK is expressed in DRG. Next, by immunocytochemistry, we show ILK’s localization both intracellularly and on the cell membrane of DRG neurons and Schwann cell precursors (SCPs). Finally, we describe ILK’s involvement in multiple aspects of DRG development by performing functional experiments in vitro. IgG-mediated interruption of ILK’s action improved DRG neurite outgrowth, modulated their directionality, stimulated SCPs migration, and impacted growth cone morphology in the presence of laminin-1 or laminin-1 mimicking peptide IKVAV. Taken together, our results show that ILK is important for chicken PNS development, probably via its exposure to the ECM.

The primary senses-touch, taste, sight, smell, and hearing-connect animals with their environments and with one another. Aside from the eyes, the primary sense organs of vertebrates and the peripheral sensory pathways that relay their inputs arise from two transient stem cell populations: the neural crest and the cranial placodes. In this chapter we consider the senses from historical and cultural perspectives, and discuss the senses as biological faculties. We begin with the embryonic origin of the neural crest and cranial placodes from within the neural plate border of the ectodermal germ layer. Then, we describe the major chemical (i.e. olfactory and gustatory) and mechanical (i.e. vestibulo-auditory and somatosensory) senses, with an emphasis on the developmental interactions between neural crest and cranial placodes that shape their structures and functions., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To determine prevalence, clinical patterns and outcomes of neurological involvement in a cohort of primary sjogren’s syndrome (PSS) patients presenting to a tertiary care hospital. Study Design: Observational retrospective cross-sectional case-control study. Place and Duration of Study: This study was carried out at Neurology department of Pak Emirates Military Hospital, Rawalpindi, from May 2015 to Jun 2016. Patients and Methods: All patients fulfilling American College of Rheumatology (ACR) criteria of PSS and having neurological involvement, who were admitted in Neurology wards from May 2015 to June 2016, were included in the study. Demographic, clinical and seroimmunological data of the patients was documented. Results: A total of 26 patients with PSS had some degree of neurological involvement. Mean age was 40.50 years. (SD 14.803, min 22, max 78). Fifteen patients were female and 11 were male. Sicca symptoms (ocular and oral dryness) were present in 38.5%. Serological marker anti Ro and La were present in 76.9% and 42.3% respectively while both Ro and La were present in 34.6%. Lip biopsy was diagnostic in 80.8% and schirmer test was positive in 46.2%. Refractory headache was present in 84.6%. Seizures occurred in 34.6%, which were focal in 23.1% and generalized in 11.5%. Trigeminal neuralgia was present in 26.9%, multiple cranial nerve palsies in 15.4% and recurrent facial nerve palsies in 11.5%. Optic neuritis was seen in 19.2%. Clinical presentation mimicking relapsing and remitting multiple sclerosis was seen in 30.8% of patients among whom 61.5% also met revised McDonald criteria for dissemination in space (DIS) on MRI and 23.1% met criteria for dissemination in time. MRI brain showed cortical lesions in 42.3%. Longitudinally extensive transverse myelitis involving cervical and upper thoracic cords was present in 26.9% of patients. Conclusion: The diagnosis of neuro-sjogren’s syndrome (NSS) can be difficult in the absence of sicca symptoms especially when neurological manifestations precede sicca symptoms by many years. This requires a high index of clinical suspicion and low threshold for investigations like lip biopsy and autoantibody profile for the diagnosis. This study highlights the need to revise the overemphasis of sicca symptoms in various current diagnostic criteria in order to improve early recognition and initiation of treatment. [ABSTRACT FROM AUTHOR]

In the peripheral nervous system (PNS) in the absence of tight blood barrier, neurons are at increased risk of DNA damage, yet the question of how effectively PNS neurons manage DNA damage remains largely unanswered. Genotoxins in systemic circulation include chemotherapeutic drugs that reach peripheral neurons and damage their DNA. Because neurotoxicity of platinum-based class of chemotherapeutic drugs has been implicated in PNS neuropathies, we utilized an in vitro model of Dorsal Root Ganglia (DRGs) to investigate how peripheral neurons respond to cisplatin that forms intra- and interstrand crosslinks with their DNA. Our data revealed strong transcriptional upregulation of the translesion synthesis DNA polymerase kappa (Pol κ), while expression of other DNA polymerases remained unchanged. DNA Pol κ is involved in bypass synthesis of diverse DNA lesions and considered a vital player in cellular survival under injurious conditions. To assess the impact of Pol κ deficiency on cisplatin-exposed DRG neurons, Pol κ levels were reduced using siRNA. Pol κ targeting siRNA diminished the cisplatin-induced nuclear Pol κ immunoreactivity in DRG neurons and decreased the extent of cisplatin-induced DNA repair synthesis, as reflected in reduced incorporation of thymidine analog into nuclear DNA. Moreover, Pol κ depletion exacerbated global transcriptional suppression induced by cisplatin in DRG neurons. Collectively, these findings provide the first evidence for critical role of Pol κ in DNA damage response in the nervous system and call attention to implications of polymorphisms that modify Pol κ activity, on maintenance of genomic integrity and neuronal function in exogenously challenged PNS. [ABSTRACT FROM AUTHOR]

Sensory neurons (SNs) detect a wide range of information from the body and the environment that is critical for homeostasis. There are three main subtypes of SNs: nociceptors, mechanoreceptors, and proprioceptors, which express different membrane proteins, such as TRKA, TRKB, or TRKC, respectively. Human pluripotent stem cell technology provides an ideal platform to study development and diseases of SNs, however there is not a viable method to isolate individual SN subtype for downstream analysis available. Here, we employ the method immunopanning to isolate each SN subtype. This method is very gentle and allows proper survival after the isolation. We use antibodies against TRKA, TRKB, and TRKC to isolate nociceptors, mechanoreceptors, and proprioceptors, respectively. We show that our cultures are enriched for each subtype and express their respective subtype markers. Furthermore, we show that the immunopanned SNs are electrically active and respond to specific stimuli. Thus, our method can be used to purify viable neuronal subtypes using respective membrane proteins for downstream studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Saito-Diaz, James, Patel and Zeltner.)

Objective: Krüppel-like Factor 7 (KLF7) is a transcription factor that promotes axon regeneration in the central nervous system. Here, we assessed whether KLF7 stimulates regeneration after peripheral nerve injury. Methods: C57BL/6 mice received an acellular nerve allograft (ANA) injected with either adeno-associated virus 2 (AAV2) vector or AAV2-KLF7 for sciatic nerve gap repair. After 4 weeks, KLF7 was detected by RT-PCR, western blot and immunohistochemistry in regenerated nerves. Axonal regeneration and functional recovery were examined by immunohistochemistry, Fluorogold (FG) and cholera toxin B (CTB) retrograde neural tracing, sciatic function index (SFI), angle of ankle, Hargreaves test and electrophysiological analysis. Results: With AAV2-KLF7 injection, KLF7 expression increased in regenerated nerves, and amplitude, score of SFI, angle of ankle and FG-labelled spinal cord neurons were increased. We observed elevated CTB-labelled neurons in dorsal root ganglia (DRG), neurofilaments, P0 (peripheral myelin) and S100 and decreased latency period and withdrawal latencies in the Hargreaves test. The SFI was significantly correlated with amplitude and regenerated axon number. Tyrosine kinase A (TrkA) and B (TrkB) receptors were also increased in the DRG. Conclusions: Our findings suggest that KLF7 promoted peripheral nerve axonal regeneration, further supporting a role for KLF7 as a growth-promoting transcription factor in the injured nervous system. [ABSTRACT FROM AUTHOR]

Highlights: [•] We developed a novel mouse neonate whole-hippocampus explant culture system to study neuronal survival, axonal outgrowth, and axonal gene and protein expression. [•] The explant culture system enables axon-specific measurements. [•] Tissue crush initially delays axonal outgrowth. [•] Axotomy does not alter instantaneous velocities up to 1h post-injury. [ABSTRACT FROM AUTHOR]

Highlights: [•] Live-cell imaging was first used to study the effect of 2,5-HD on slow axonal transport in vitro. [•] GFP-tagged protein and fluorescence microscope were used to explore NF-M transport. [•] 2,5-HD impaired the levels of motor proteins associated with NF-M transport in DRG cells. [•] 2,5-HD reduced ATP levels in DRG cells, which provides energy support for NF-M transport. [ABSTRACT FROM AUTHOR]

Introduction: Neurological involvements were shown in 20% of patients with Primary Sjogren's Syndrome (pSS). Neurological symptoms may be the first signs of pSS in 57% of the cases. In addition, early diagnosis and treatment of neurological disorders may save or improve the quality of life of these cases. There have been reports about the neurologic manifestations of pSS but little is known about the details of neurologically presented cases. Method: In this study, we described 11 pSS patients who presented with neurological manifestations. Results: Central nervous system (CNS) involvement was recorded in 7 (63.7%) and peripheric nervous system (PNS) involvement in 4 cases (36.4%). Conclusion: Our findings regarding the cases with neurological manifestations leading to the diagnosis of pSS suggest that: 1) The frequency of CNS involvement was higher than that of PNS, and the most frequent clinical pictures of CNS involvement are Multiple Sclerosis (MS)-like illnesses and optic neuritis, 2) Guillain Barre Syndrome (GBS) was the most frequent disease of PNS involvement; 3) Mononeuropathy multiplex (MM) might be the first sign of pSS; 4) Neurologists should consider pSS in the differential diagnosis of cases with MS, optic neuritis, GBS and neuropathies of unknown causes including MM; 5) There is an urgent need of therapeutical guidelines for the cases with neurological involvement associated with pSS. [ABSTRACT FROM AUTHOR]

Highlights: [•] Oligodendrocyte cell death and demyelination are common after spinal cord injury. [•] Myelin helps sustain axonal homeostasis; demyelinated axons are prone to degenerate. [•] Remyelination is slow but complete after spinal cord injury. [•] The value of accelerating remyelination after spinal cord injury is still unclear. [•] Many strategies to promote remyelination are unexplored after spinal cord injury. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ten days post EAE induction, mice had reduced pain thresholds. [•] GFAP expression was increased in SGCs in DRG of 10-day EAE mice. [•] Coupling among SGCs was increased in DRG of 10-day EAE mice. [ABSTRACT FROM AUTHOR]

Abstract: A differential role of endothelin-1 (ET-1) in pain processing has recently been suggested. However, the function of central ET-1 in neuropathic pain (NP) has not been fully elucidated to date. We report here the action of endogenous central ET-1 in sciatic nerve ligation-induced NP (SNL-NP) in a transgenic animal model that over-expresses ET-1 in the astrocytes (GET-1 mice). We hypothesized that the over-expression of astrocytic ET-1 would exert anti-allodynic and anti-hyperalgesic effects in NP, as demonstrated by mechanical threshold and plantar withdrawal latency using the von Frey filament and heat stimuli. In our animal model, GET-1 mice showed an increase in the withdrawal threshold and latency in response to the mechanical and thermal stimuli, respectively, in pain behavior tests after SNL. ET-1 and endothelin type A receptor (ETA-R) levels were increased significantly in L4–L6 segments of the spinal cord (ipsilateral to SNL) of GET-1 mice at 7 and 21days after surgery. Moreover, intrathecal administration of a specific ETA-R antagonist, BQ-123, attenuated the anti-allodynic and anti-hyperalgesic phenotype in GET-1 mice. The effects of BQ-123 on the mRNA expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase B/serine protein kinase (Akt(s)) were assessed in the ipsilateral L4–L6 segments harvested 30min after BQ-123 administration on day 7 after surgery. Phosphorylation of ERK1/2 and Akt(s) in the ipsilateral spinal cord of GET-1 mice was reduced following SNL, whereas no reduction was observed after intrathecal injection of BQ-123. In conclusion, our results showed that the xover-expression of astrocytic ET-1 reduced SNL-induced allodynia and hyperalgesia by inhibiting the activation of ERK1/2 and Akt(s) via the ETA-R-mediated pathway. [Copyright &y& Elsevier]

Abstract: Mitochondrial degeneration is considered to play an important role in the development of diabetic peripheral neuropathy in humans. Mitochondrial degeneration and the corresponding protein regulation associated with the degeneration were studied in an animal model of diabetic neuropathy. PGC-1α and its-regulated transcription factors including TFAM and NRF1, which are master regulators of mitochondrial biogenesis, are significantly downregulated in streptozotocin diabetic dorsal root ganglion (DRG) neurons. Diabetic mice develop peripheral neuropathy, loss of mitochondria, decreased mitochondrial DNA content and increased protein oxidation. Importantly, this phenotype is exacerbated in PGC-1α (−/−) diabetic mice, which develop a more severe neuropathy with reduced mitochondrial DNA and a further increase in protein oxidation. PGC-1α (−/−) diabetic mice develop an increase in total cholesterol and triglycerides, and a decrease in TFAM and NRF1 protein levels. Loss of PGC-1α causes severe mitochondrial degeneration with vacuolization in DRG neurons, coupled with reduced state 3 and 4 respiration, reduced expression of oxidative stress response genes and an increase in protein oxidation. In contrast, overexpression of PGC-1α in cultured adult mouse neurons prevents oxidative stress associated with increased glucose levels. The study provides new insights into the role of PGC-1α in mitochondrial regeneration in peripheral neurons and suggests that therapeutic modulation of PGC-1α function may be an attractive approach for treatment of diabetic neuropathy. [Copyright &y& Elsevier]

Abstract: Glycans attached to the cell surface via proteins or lipids or exposed in the extracellular matrix affect many cellular processes, including neuritogenesis, cell survival and migration, as well as synaptic activity and plasticity. These functions make glycans attractive molecules for stimulating repair of the injured nervous system. Yet, glycans are often difficult to synthesize or isolate and have the disadvantage to be unstable in a complex tissue environment. To circumvent these issues, we have screened a library of small organic compounds to search for structural and functional mimetics of the neurostimulatory glycan polysialic acid (PSA) and identified the 5-HT4 receptor agonist tegaserod as a PSA mimetic. The PSA mimicking activity of tegaserod was shown in cultures of central and peripheral nervous system cells of the mouse and found to be independent of its described function as a serotonin (5-HT4) receptor agonist. In an in vivo model for peripheral nerve regeneration, mice receiving tegaserod at the site of injury showed enhanced recovery compared to control mice receiving vehicle control as evidenced by functional measurements and histology. These data indicate that tegaserod could be repurposed for treatment of nervous system injuries and underscores the potential of using small molecules as mimetics of neurostimulatory glycans. [Copyright &y& Elsevier]

Highlights: [•] We propose chrysin is a potent anti-inflammatory and neuroprotective agent for EAN. [•] Chrysin reduced inflammatory cell infiltration and demyelination of sciatic nerves. [•] Chrysin inhibited the expression of iNOS and COX-2 via suppressing NF-κB pathway. [•] Chrysin depressed levels of pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Abstract: Mutations of several genes encoding peroxisomal proteins have been associated with human diseases. Some of these display specific white matter abnormalities in the brain, although the affected proteins are ubiquitously expressed. To better understand the etiology of peroxisomal myelin diseases, we aimed to label these organelles in vivo and in a cell type specific fashion. We had previously shown that in oligodendrocytes and Schwann cells numerous peroxisomes reside in the cytoplasmic channels of “non-compacted” myelin. These organelles are smaller and biochemically distinct from non-myelin peroxisomes. Targeting peroxisomal functions in various cell types of the brain has demonstrated that oligodendroglial peroxisomes are specifically important for long-term integrity of the CNS. To visualize myelin peroxisomes in intact cells and tissues by live imaging, we have generated a novel line of transgenic mice for the expression of fluorescently tagged peroxisomes specifically in myelinating glia. This was achieved by modifying the gene for a photoconvertible mEos2 with a peroxisomal targeting signal type 1 (PTS1) and generating a fusion gene with the myelin-specific Cnp1 promoter. In the brain of resulting transgenic mice, peroxisomes are selectively labeled in oligodendrocytes. In this novel genetic tool, photoconversion of single peroxisomes from green to red fluorescence can be used to monitor the fate of single organelles and to determine the dynamics of PTS1-mediated protein import in the context of myelin diseases that affect peroxisomal functions. [Copyright &y& Elsevier]

Highlights: [•] Nervous system adapts its local levels of pregnenolone, progesterone and its metabolites in response to changes in gonadal hormones. [•] Progesterone and its metabolites act as physiological modulators and protective agents in the nervous system. [•] Levels of progesterone and its metabolites are affected in neurodegenerative diseases. [•] Levels of progesterone and its metabolites in the nervous system are sex-dimorphic. [•] It is possible to increase locally the levels of progesterone and its metabolites by pharmacological approaches. [ABSTRACT FROM AUTHOR]

Highlights: [•] Progesterone is present in females and in males. [•] Adrenal progesterone secretion is increased by stress. [•] In response to injury, progesterone is increased in the brain. [•] Progesterone receptors play a key role in neuroprotection and myelin repair. [•] Therapeutic promises for progestins as neuroprotective and remyelinating agents. [ABSTRACT FROM AUTHOR]

Abstract: Nogo-A is a major form of growth inhibitory molecule (growth-IM) which inhibits axonal regeneration and neurite regrowth after neural injury. Bone marrow stromal cells (MSCs) have been shown to inhibit Nogo-A expression in vitro and in cerebral ischemic animal models. The present study was designed to investigate the effects of treatment with human MSCs (hMSCs) impregnated into collagen scaffolds on the expression of Nogo-A and axonal plasticity after traumatic brain injury (TBI). Adult male Wistar rats were injured with controlled cortical impact and treated either with saline, hMSCs-alone or hMSCs impregnated into collagen scaffolds (scaffold+hMSC) transplanted into the lesion cavity 7 days after TBI. Rats were sacrificed 14 days after TBI and brain tissues were harvested for immunohistochemical studies, Western blot analysis, laser capture microdissections and qRT-PCR to evaluate axonal density and Nogo-A protein and gene expressions. Our data showed that treatment of TBI with scaffold+hMSC significantly decreased TBI-induced Nogo-A protein expression and increased axonal density compared to saline and hMSC-alone treatments. In addition, scaffold+hMSC transplantation decreased Nogo-A transcription in oligodendrocytes after TBI. Scaffold+hMSC treatment was superior to hMSC-alone treatment in suppressing Nogo-A expression and enhancing axonal regeneration after TBI. Our data suggest that transplanting hMSCs with scaffolds down-regulates Nogo-A transcription and protein expression which may partially contribute to the enhanced axonal regeneration after TBI. [Copyright &y& Elsevier]

Highlights: [•] Glutamate is released from trigeminal SGCs through EAATs. [•] Elevated glutamate in TG excites ganglion neurons through NMDA receptors. [•] Blocking glutamate uptake in the TG increases neuronal discharge. [•] Mechanical sensitization of muscle nociceptors is induced by elevated glutamate in the TG. [•] Mechanical sensitization is due to a peripheral mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) have been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-1, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development. [Copyright &y& Elsevier]

Abstract: Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed. [Copyright &y& Elsevier]

Abstract: Objective: Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop obesity, dyslipidemia, moderate hypertension, hyperinsulinemia and impaired glucose tolerance prone to induce peripheral neuropathy (PN). Autophagy has been shown to prevent neurodegeneration in the central and peripheral nervous system. We analyzed the potential protective role of autophagy in an established rat model in preventing PN. Methods: We examined electrophysiology (motor-and sensory/mixed afferent conduction velocities and the minimal F-wave latency) and morphology, including ultrathin sections, myelin sheath thickness (g-ratio) and immunohistochemical markers of autophagy and inflammation in the sciatic nerve of five-month-old, male WOKW as compared to Wistar derived, congenic LEW.1W control rats, characterized by the same major histocompatibility complex as WOKW rats (RT1u). Moreover, the expression of axonal and synaptic proteins (NF68, GAP43, MP0), autophagy- (Atg5, Atg7, LC3), and apoptosis (cleaved caspase-3)-related markers was measured using Western blot. Results: No abnormalities in nerve electrophysiology and morphology were found in WOKW compared to LEW.1W rats. However, autophagosomes were more frequently apparent in sciatic nerves of WOKW rats. In Western blot analyses no significant differences in expression of neuronal structural proteins were found, but autophagy markers were up-regulated in WOKW compared to LEW.1W sciatic nerves. Immunostaining revealed a greater infiltration of Iba1/ED-1-positive macrophages, CD-3-positive T-cells and LC3-expression in sciatic nerves of WOKW rats. Conclusions: Our results indicate that WOKW rats show an up-regulated autophagy and a mild inflammatory response but do not develop overt neuropathy. We suggest that autophagy and inflammatory cells may exert a protective role in preventing neuropathy in this rat model of the metabolic syndrome but the mechanism of action is still unclear. [Copyright &y& Elsevier]

Highlights: [•] AQP1 gene silencing leads to Schwann cells shrinkage. [•] AQP1 overexpression leads to Schwann cells swelling. [•] AQP1 knockdown caused the Schwann cells to resist edema following hypoxia. [•] HIF-1α participates in the hypoxic induction of the AQP1 gene. [•] AQP1 inhibition might provide a new treatment options for peripheral nerve edema. [Copyright &y& Elsevier]

Abstract: Mobilization of remyelinating cells spontaneously occurs in the adult brain. These cellular resources are specially active after demyelinating episodes in early phases of multiple sclerosis (MS). Indeed, oligodendrocyte precursor cells (OPCs) actively proliferate, migrate to and repopulate the lesioned areas. Ultimately, efficient remyelination is accomplished when new oligodendrocytes reinvest nude neuronal axons, restoring the normal properties of impulse conduction. As the disease progresses this fundamental process fails. Multiple causes seem to contribute to such transient decline, including the failure of OPCs to differentiate and enwrap the vulnerable neuronal axons. Regenerative medicine for MS has been mainly centered on the recruitment of endogenous self-repair mechanisms, or on transplantation approaches. The latter commonly involves grafting of neural precursor cells (NPCs) or neural stem cells (NSCs), with myelinogenic potential, in the injured areas. Both strategies require further understanding of the biology of oligodendrocyte differentiation and remyelination. Indeed, the success of transplantation largely depends on the pre-commitment of transplanted NPCs or NSCs into oligodendroglial cell type, while the endogenous differentiation of OPCs needs to be boosted in chronic stages of the disease. Thus, much effort has been focused on finding molecular targets that drive oligodendrocytes commitment and development. The present review explores several aspects of remyelination that must be considered in the design of a cell-based therapy for MS, and explores more deeply the challenge of fostering oligodendrogenesis. In this regard, we discuss herein a tool developed in our research group useful to search novel oligodendrogenic factors and to study oligodendrocyte differentiation in a time- and cost-saving manner. [Copyright &y& Elsevier]